Are visual outcomes satisfactory after endoscopic endonasal transsphenoidal surgery in elderly patients with non-functioning pituitary adenomas?

Are visual outcomes satisfactory after endoscopic endonasal transsphenoidal surgery in elderly patients with non-functioning pituitary adenomas? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Are visual outcomes satisfactory after endoscopic endonasal transsphenoidal surgery in elderly patients with non-functioning pituitary adenomas? Kiyohiko Sakata, Aya Hashimoto, Masatoshi Haruta, Yoshinori Hashimoto, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7319844/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Non-functioning pituitary adenomas (NFPA) in elderly patients may be followed conservatively because of a limited life expectancy, except when visual function is severely impaired. A decision to perform surgical intervention in these patients should be supported by favorable surgical and visual outcomes. Methods Data were analyzed for 130 patients with NFPA treated surgically since 2010. Patients aged ≥ 75 years (elderly group) were compared with non-elderly patients aged < 74 years regarding patient characteristics, tumor characteristics, surgical and visual outcomes, and preoperative visual function, including disease duration and ophthalmologic comorbidities. Results Visual impairment was highly prevalent in the 22 elderly patients with NFPA. However, postoperative visual improvement occurred in only 47.6% of these symptomatic patients, which was significantly poorer than that in non-elderly patients ( p < 0.01). Furthermore, two of three patients who developed postoperative suprasellar hematoma after surgery experienced visual deterioration. In elderly patients, a high prevalence of ophthalmologic comorbidities and previous cataract surgery were associated with delayed surgery ( p < 0.01). Additionally, patients aged 65–74 years had a higher prevalence of ophthalmologic comorbidities and preceding cataract surgery than patients aged < 64 years ( p 0.05). Conclusion Several issues are associated with visual outcomes when performing surgery in elderly patients with NFPAs. Early surgical intervention after the onset of visual symptoms due to NFPA is desirable, and particular care is necessary to avoid postoperative suprasellar hematoma. elderly patient non-functioning pituitary adenoma visual outcome cataract disease duration postoperative suprasellar hematoma transsphenoidal surgery Figures Figure 1 Introduction Pituitary adenomas are relatively common tumors with a reported prevalence of 14–23% in various autopsy or radiologic studies, accounting for 5–20% of all intracranial tumors [1–4]. Elderly patients account for up to 14% of all patients diagnosed with pituitary tumors, with most lesions being non-functioning pituitary adenomas (NFPAs) [5]. Increased life expectancy in the general population is causing rapid growth in the number of elderly persons, and the number of those diagnosed with NFPAs could continue to rise [6]. The number of elderly persons, defined by the World Health Organization as those ≥ 65 years of age, is projected to reach 2.2 billion globally by the late 2070s, surpassing the number of children (under age 18 years). Despite the fact that the estimated total population worldwide has been revised downward compared with previous estimates, the proportion of elderly persons is likely to grow rapidly, nearly doubling between 2024 and 2054, and could comprise one third or more in many developed countries by 2054 [7]. The Japan Federation of Gerontological Societies recommends a definition of ≥ 75 years of age for “elderly” since 2017 because the general population in Japan is already considered elderly [8]. Overall, patients with NFPA present with visual acuity and field dysfunction at an incidence of 13.0–60.8% [9]; visual dysfunction is the most frequent presentation in elderly patients, with an incidence of 60–80% [10]. Therefore, the reason for surgery in patients with NFPA is improvement of visual function as a result of compression of the anterior visual pathways involving the optic chiasma and optic nerves [11, 12]. However, the diagnosis of NFPA in the elderly is usually delayed because visual symptoms may not be recognized and can be attributed to aging or concurrent ophthalmologic diseases [13–16]. Recent studies have reported that endoscopic endonasal transsphenoidal surgery (TSS) for NFPA is well-tolerated and feasible in elderly patients [5, 12, 13, 17–20]. However, some studies have shown higher complication rates in elderly versus non-elderly patients [6, 16, 21–24]. Therefore, a decision to perform surgical intervention for elderly patients with NFPA should be supported by postoperative favorable visual outcomes. We retrospectively evaluated surgical and visual outcomes in elderly patients with NFPA, compared with outcomes in non-elderly patients. Materials and Methods Study design This was a case–control study examining the clinical characteristics and postoperative visual outcomes of elderly patients who underwent surgery for NFPA. The patients’ clinical variables and surgical case details were compared between elderly patients and non-elderly patients to identify factors that may contribute to visual outcomes. Patients and data collection and settings We enrolled and analyzed the data of 130 consecutive patients with NFPA who were treated surgically in our institution from January 2010 to December 2024. Patients were identified from the clinical records of those with a diagnosis of pituitary adenoma on the basis of clinical history and presentation, imaging studies, and hormone workup. Patients with non-pituitary adenoma and functional pituitary adenoma pathologies were excluded. This study was approved by the Ethics Committee of the Kurume University School of Medicine (approval number: 18019), and the study was performed in accordance with the guidelines of the Declaration of Helsinki. All participants provided informed consent to undergo the proposed treatment after all options for the management of NFPA had been clearly explained, and all patients agreed to participate in the study. The overall cohort was divided into an elderly group (aged ≥ 75 years) and a non-elderly group (aged < 74 years). The latter was further divided into younger patients (aged < 64 years) and pre-old patients (65–74 years). Clinical and surgical variables collected from the patients’ medical charts comprised age, proportion of men/women, preoperative visual symptoms, preoperative hypopituitarism, maximum tumor size, cavernous sinus invasion (Knosp grade 4) [25], surgical approach, history of previous pituitary surgery, pathological diagnosis, resection rate, and postoperative complications. The pathological diagnosis was divided into the aggressive variant (tumors formerly diagnosed as “atypical adenoma,” Crooke’s cell tumors, silent corticotroph tumors, and immature PIT-1 lineage tumors) and the common variant (gonadotroph tumors, other silent tumors, and null cell tumors) [26–30]. Regarding the resection rate, gross total resection was defined as complete tumor disappearance on postoperative magnetic resonance imaging. Subtotal resection was defined as > 90% removal of the tumor on magnetic resonance imaging, and tumor resection of < 90% was defined as partial resection. Preoperative hypopituitarism was defined as a requisite status of pituitary replacement therapy with hydrocortisone and/or levothyroxine sodium hydrate owing to pituitary apoplexy, previous surgeries, and symptomatic hypopituitarism caused by tumor growth. Postoperative complications that occurred within 30 days after surgery were recorded, including cerebrospinal fluid (CSF) leakage requiring surgical repair, new cranial nerve deficit, postoperative infection, delayed massive epistaxis, postoperative symptomatic suprasellar hematoma, development of permanent arginine vasopressin deficiency, and new postoperative hypopituitarism requiring continuous administration of hydrocortisone and/or levothyroxine sodium hydrate. In patients with preoperative visual impairment, we investigated the severity before surgery (defined as severe if the visual acuity of either eye was ≤ 0.1), presence of ophthalmologic comorbidities, cataract surgery prior to pituitary tumor surgery, and disease duration (except for patients who were not clearly aware of the onset of the disease). Postoperative visual outcomes were simply classified into three categories; improved, unchanged, and deteriorated, on the basis of the results of ophthalmological examination performed before and 2 weeks after surgery. Cases in which visual function improvement was not achieved were reevaluated 3 or 6 months after surgery. The final decision on visual outcomes was based on the ophthalmologist’s judgment. The status of “improved” included any visual field improvement even if there was no clear improvement in visual acuity. If the patient reported no subjective improvement when the changes in the ophthalmological results were equivocal, the results were considered “unchanged.” If there was any deterioration in either visual acuity or visual field, the results were considered “worsened.” We also investigated long-term outcomes regarding postoperative tumor control in our surgical cases in which sufficient follow-up data were available after discharge. Planned radiotherapy, whether stereotactic radiosurgery or intensity-modulated radiotherapy, for residual tumors, especially in the cavernous sinus or invasive tumors, was defined as treatment administered within 6 months after surgery. Outcomes were classified by the three age groups and categorized as follows: (1) no tumor recurrence or regrowth, (2) wait and scan for tumor regrowth after incomplete resection (subtotal resection/partial resection), (3) wait and scan for tumor recurrence after gross total resection, (4) addition of radiotherapy for tumor recurrence or regrowth, (5) required surgery for tumor recurrence or regrowth, and (6) required surgery followed by radiotherapy. Surgical methods The surgical approaches were classified into usual endoscopic endonasal TSS via the enlarged sellar turcica, transcranial surgery that included simultaneous combined surgery with TSS, and endoscopic endonasal extended TSS that required opening of the tuberculum sellae and planum sphenoidale for a suprasellar tumor component. Transcranial surgery and simultaneous combined surgery were performed for giant tumors with multilobular extension. Extended TSS was performed for tumors that extended into the subfrontal area along the planum sphenoidale or tumors that had coalesced with suprasellar neurovascular structures. Sellar floor reconstruction was performed gradually using consolidated methods on the basis of the degree of intraoperative CSF leakage using thigh fat and fascia, bone pieces from the nasal septum, and vascularized nasoseptal flaps [31]. Perioperatively, antiplatelet therapy and/or anticoagulant therapy were discontinued in all cases. Statistical analysis Normally distributed data were expressed as mean ± standard deviation (minimum–maximum values). For categorical variables, groups were compared using Fisher’s exact test. For normally distributed continuous datasets, the groups were compared using Student’s t -test. Multivariate logistic regression analysis was performed using significant categorical variables to identify predictive factors for postoperative visual improvement. A p value of < 0.05 was considered statistically significant, and statistical analyses were performed using JMP Student Edition (SAS Institute Inc., Cary, NC, USA). Results Clinical presentation The cohort included 22 elderly patients. The patients’ background data were compared with those of the remaining 108 non-elderly patients (Table 1 ). There were no statistically significant differences between the groups in the proportions of men/women, maximum tumor diameter, cavernous sinus invasion, status of preoperative pituitary replacement therapy, history of previous pituitary surgery, pathological diagnosis, and resection rate. Notably, preoperative visual dysfunction was a chief complaint in most elderly patients, and the prevalence was significantly different compared with non-elderly patients. The only patient without visual impairment had a tumor that extended beyond the sphenoid sinus and filled the nasal cavity, which was treated surgically to relieve nasal obstruction. Extended TSS was selected significantly more often in the elderly than non-elderly group ( p = 0.021), and invasive surgical treatments were avoided, such as simultaneous combined surgeries. However, half of the cases in which extended TSS was selected were switched from standard TSS during surgery because with suprasellar tumors, it was difficult to dissect into the sellar space due to adhesions, even though the tumors were not particularly large. Table 1 Comparison of characteristics between elderly and non-elderly groups of patients with non-functioning pituitary adenomas Age, years Elderly group (≥ 75) Non-elderly group (< 74) p value Number of patients 22 108 Age at diagnosis, years 78.5 ± 3.2 (range: 75–85) 55.2 ± 13.1 (range: 17–74) <0.01 Sex, male:female 11 : 11 57 : 51 0.820 Preoperative visual dysfunction 95.5% (Yes: 21, No: 1) 67.6% (Yes: 73, No: 35) <0.01 Preoperative pituitary dysfunction 28.6% (Yes: 6, No: 16) 22.3% (Yes: 24, No: 84) 0.588 Maximum tumor diameter, mm 33.7 ± 9.9 (range: 18–65) 31.1 ± 10.2 (range: 11–63) 0.265 Giant adenoma (≥ 40 mm) 18.2% (Yes: 4, No: 18) 16.7% (Yes: 18, No: 90) 1.000 Cavernous sinus invasion , Knosp grade Grade 0–2: 13 Grade 3: 3 Grade 4: 6 Grade 0–2: 68 Grade 3: 26 Grade 4: 14 0.811 0.107 Past history of pituitary surgery 19.0% (Yes: 4, No: 18) 9.7% (Yes: 11, No: 97) 0.283 Pathological diagnosis Common variant: 19 Aggressive variant: 3 Common variant: 100 Aggressive variant: 8 0.396 Surgical approach eTSS: 16 Extended eTSS: 6 TCS or combined TCS + eTSS: 0 eTSS: 92 Extended eTSS: 9 TCS or combined TCS + eTSS: 7 0.208 0.021 Extent of tumor resection GTR: 13 STR: 6, PR: 3 GTR: 78 STR: 22, PR: 8 0.307 Surgical complications 19.0% (Yes: 5, No: 17) 11.1% (Yes: 12, No: 96) 0.165 Newly developed hypopituitarism: 1 Severe meningitis: 1 Postoperative suprasellar hematoma: 3 Newly developed hypopituitarism*: 2 Newly developed pAVPD: 5 CSF leakage*: 4 Delayed epistaxis: 2 Data are presented as n or mean ± standard deviation (range) unless otherwise indicated. Groups were compared using Fisher’s exact test or the chi-square test, as appropriate. Boldface p values are statistically significant. *One patient developed both CSF leakage and newly developed partial hypopituitarism. CSF: cerebrospinal fluid, eTSS: endoscopic transsphenoidal surgery, GTR: gross total resection, pAVPD: permanent arginine vasopressin deficiency, PR: partial resection, STR: subtotal resection, TCS: transcranial surgery. Postoperative complications The postoperative complications differed remarkably between the elderly and non-elderly groups. In non-elderly patients, newly developed hypopituitarism required oral replacement therapy in two patients, permanent arginine vasopressin deficiency occurred in five patients, postoperative CSF leakage required surgical repair in four patients, and delayed massive epistaxis occurred in two patients. In elderly patients, newly developed hypopituitarism occurred in one patient, severe meningitis that required intensive care occurred in one patient, and postoperative symptomatic suprasellar hematoma occurred in three patients. Among the three patients with postoperative hematoma (two of whom had recurrent adenomas), two required emergency reoperation the day after the initial surgery because of severe visual impairment; the remaining patient was treated conservatively. The patient who was treated conservatively developed transient bitemporal hemianopsia but recovered to the preoperative state. The two patients who underwent reoperation developed visual deterioration but recovered to better vision quality than that before reoperation. All of these patients returned to their previous lives without hormonal replacement therapy. There was no mortality within 30 days after surgery in either group. A representative case is shown in Fig. 1 . Postoperative visual outcomes and concurrent ophthalmologic comorbidities When we compared the clinical characteristics between the elderly and non-elderly groups in patients with preoperative visual dysfunction, there were significant differences in the severity of visual impairment before surgery, disease duration (especially > 1 year), prevalence of ophthalmologic comorbidities, and history of previous cataract surgery (Table 2 ). Visual outcomes were significantly less favorable in elderly patients than in non-elderly patients ( p < 0.01). Despite sufficient tumor decompression, 8 of the 10 patients who showed no changes in visual function after surgery had a longer disease duration of several years. Six patients had glaucoma and were undergoing long-term eye-drop treatment, and four did not recover their visual function after pituitary surgery. Among 13 patients who had a history of previous cataract surgery, 9 had undergone cataract surgery after the onset of NFPA-related symptoms and experienced an unexpected course after cataract surgery and progression of visual symptoms. These were complex factors that delayed the timing of pituitary surgery, although the maximum tumor size was > 30 mm in all patients. Furthermore, among elderly patients whose postoperative visual function was unchanged compared with preoperative function, none required additional ophthalmologic treatment, including cataract surgery, for further visual recovery after pituitary surgery. Table 2 Differences in preoperative visual status, disease duration, ophthalmologic comorbidities, and visual outcomes, stratified by age Age, years Elderly group (≥ 75) Non-elderly group (< 74) p value Pre-old (≥ 65) Younger (< 64) Number of patients with visual symptoms 21 73 22 51 Sex, male:female 10 : 11 39 : 34 0.805 10 : 12 29 : 22 0.447 Preoperative severe visual status* Yes: 8 No: 13 Yes: 11 No: 62 0.031 Yes: 4 No: 18 Yes: 7 No: 44 0.724 Median disease duration** 18 months 8 months 1 year 57.1% (Yes: 12, No: 9) 20.5% (Yes: 15, No: 58) 0.002 18.2% (Yes: 4, No: 18) 21.6% (Yes: 11, No: 40) 1.000 Ophthalmologic comorbidities 85.7% (Yes: 18, No: 3) 23.3% (Yes: 15, No: 58) < 0.01 50.0% (Yes: 11, No:11) 11.8% (Yes: 4, No: 47) <0.01 Previous cataract surgery (% after NFPA onset) 61.9% (61.5% after onset) 8.2% <0.01 27.2% (66.7% after onset) 0.0% <0.01 Postoperative visual outcome Improved: 47.6% Unchanged: 42.9% Worsened: 9.5% Improved: 90.4% Unchanged: 8.2% Worsened: 1.4% <0.01 Improved: 91.0% Unchanged: 4.5% Worsened: 4.5% Improved: 90.2% Unchanged: 9.8% Worsened: 0% 1.00 Data are presented as n unless otherwise indicated. Groups were compared using Fisher’s exact test or the chi-square test, as appropriate. Boldface p values are statistically significant. *Cases in which vision in either the left or right eye decreased to ≤ 0.1. **Excluding eight patients in whom disease onset was unclear because they were unaware of their visual impairment. These patients were considered to have a short disease duration for visual symptoms. NFPA: non-functioning pituitary adenoma. When we compared differences between the younger group and the pre-old group, there were also statistically significant differences in the prevalence of ophthalmologic comorbidities and previous cataract surgery. However, favorable visual outcomes were achieved, with no statistically significant differences in disease duration and the severity of visual impairment before surgery between the two groups. In the pre-old group, cataracts were present in 8 of 11 patients with ophthalmologic comorbidities. Six had undergone cataract surgery before pituitary surgery (four underwent cataract surgery after NFPA-related symptom onset), and the median disease duration for these six patients was 10.5 months. Predictive factors associated with postoperative visual improvement We also investigated the data of 91 patients with preoperative visual impairment, except for 3 patients with deteriorated vision after surgery, to determine whether postoperative vision was improved or unchanged. Multivariate logistic regression analysis revealed that disease duration > 1 year and age at presentation ≥ 75 years were independent predictors of postoperative visual improvement (Table 3 ). Table 3 Postoperative long-term disease outcomes during follow-up, stratified by age Age, years Elderly (≥ 75) Pre-old (65–74) Younger (< 64) Number of treated patients 22 38 70 Eligibility* 20 36 67 % residual (STR/PR) tumor 45.0% 25.0% 28.4% % Recurrent tumor 20.0% 11.1% 7.5% % Knosp grade 4 tumor 30.0% 8.3% 14.9% % Aggressive variant 10.0% 5.6% 9.0% Planned radiotherapy** 0 0 4 Long-term disease outcome No tumor recurrence/regrowth 19 32 59 Wait and scan for regrowth 1 2 3 Wait and scan for recurrence 0 1 1 Radiotherapy 0 0 3 Required surgery 0 0 1 Surgery followed by radiotherapy 0 1 0 Median follow-up period (range) 31.5 months (6–93 months) 62 months (6–160 months) 60 months (6–169 months) Data are presented as n unless otherwise indicated. *Eligibility for long-term assessment was defined as patients who were followed up radiologically for > 6 months. **These patients received radiotherapy within 6 months after surgery. STR: subtotal resection, PR: partial resection. Long-term disease control and further treatment Of the eligible patients who were followed for > 6 months, 123 patients were followed for a median of 60.0 months (Table 4 ). Despite the high rates of residual tumors, recurrent tumors, and aggressive variants in the elderly group, no cases required additional treatment. Furthermore, in the pre-old group, all patients could be followed conservatively after surgery during follow-up, except for one case with former “atypical adenoma” that recurred 3 years after surgery. This patient underwent extended TSS followed by radiotherapy. In the younger group, seven patients required additional radiotherapy for residual tumors inside the cavernous sinus or for widely invading residual tumors. One younger patient underwent surgery for early cystic recurrence after subtotal resection but had no evidence of disease > 10 years after reoperation. Overall, 89.4% of the patients showed no recurrence. Table 4. Multivariable logistic regression analysis of predictive factors for postoperative visual improvement Entire cohort Categorical variant Odds ratio 95% CI p value Age at presentation < 75 years 6.439 1.58–28.4 0.0093 Disease duration < 1 year 9.329 2.49–41.3 0.0008 Non-severe visual impairment at presentation 1.361 0.26–6.45 0.7042 Elderly and pre-old patient groups Categorical variant Odds ratio 95% CI p value Age at presentation < 75 years 19.488 2.14–541.2 0.0061 Disease duration < 1 year 6.596 1.01–60.9 0.0483 Absence of ophthalmological comorbidities 0.359 0.02–4.17 0.4051 CI: confidence interval. Discussion In this study, we showed that visual outcomes after endoscopic TSS surgery for NFPA in the elderly group were significantly poorer than those in the non-elderly group. This is an important result for clinicians. In NFPA patients presenting with visual dysfunction, 56.4–90.0% reported improved vision postoperatively [9]. Additionally, previous studies of visual outcomes after endoscopic TSS revealed that favorable visual outcomes were affected by age, preoperative severity of the visual status, and disease duration [32–37]. The visual recovery rate in elderly patients in these studies, most of which used a cut-off value of 65 or 70 years of age, was not significantly different compared with non-elderly patients and ranged from 78.5–91.0% [5, 6, 11, 12, 16, 19, 20, 23]. However, the visual recovery rate in several studies was < 67% [17, 18, 38, 39], and a series reported by Pereira et al. [39] reported a rate of only 41.2% for visual improvement in 102 patients aged ≥ 70 years. Several factors may account for the wide variability in visual outcomes following endoscopic TSS for NFPAs in elderly patients. One possible explanation is a delayed diagnosis of the NFPA or prolonged disease duration prior to surgical intervention. Given the high prevalence of cataracts in this age group, optic nerve atrophy secondary to an NFPA may be obscured by lens opacity, potentially resulting in delayed diagnosis [11]. Gerges et al. [40] reported that among patients aged ≥ 50 years with NFPAs and visual impairment, 18.0% had cataracts and 12.5% underwent cataract surgery, a rate significantly higher than the national prevalence of cataract surgery (5.1%). Consistent with these findings, a substantial proportion of patients in our cohort had undergone cataract surgery prior to pituitary surgery. It is plausible that visual impairment caused by an NFPA was initially misattributed to cataracts. Consequently, cataract surgery was performed, but the anticipated visual improvement was not achieved. A subsequent comprehensive ophthalmologic and neurologic evaluation ultimately led to the correct diagnosis of an NFPA. Furthermore, several patients in our cohort had previously been treated for glaucoma. The visual field constriction associated with glaucoma may have masked the characteristic bitemporal hemianopia and/or central scotoma caused by the NFPA, thereby complicating early detection. In patients with a delayed diagnosis, postoperative visual recovery is not guaranteed—even with sufficient decompression of the optic apparatus—and blindness may develop if surgery is not planned in a timely manner. Jahangiri et al. [15] found that symptom duration of ≤ 6 months was significantly associated with recovery to baseline visual function, whereas neither age at diagnosis nor symptom duration was a significant predictor of postoperative visual improvement. Notably, age was significantly associated with symptom duration. Butenschoen et al. [33] reported that the strongest predictor of improvement of visual acuity after transsphenoidal tumor resection was age, which was most likely correlated with longer disease duration and the high prevalence of ophthalmologic comorbidities. Thus, several researchers have referred to the correlation between long symptom duration and ophthalmologic comorbidities in elderly patients regarding postoperative visual outcomes [13–16]. However, our study is the first to our knowledge to confirm the statistically significant relationship between these factors and postoperative visual outcomes using pre- and postoperative datasets. The results of the multivariate analysis also showed that not only symptom duration but also aging were independent factors associated with postoperative visual improvement, which may be related to reduced physiological plasticity in neural function recovery specific to elderly patients [41]. Barzaghi et al. [32] reported that preoperative visual impairment was more severe in cases with a disease duration of ≥ 12 months and in patients aged ≥ 50 years. This finding suggests that younger patients are better able to compensate for microvascular deprivation due to tumor compression of small vessels that feed the chiasmatic crossing fibers from inferior aspects [32]. Notably, Wilson et al. [24] stated that elderly patients may be at increased risk of postoperative visual deterioration independent of surgical technique. Another reason for unfavorable visual outcomes in elderly patients after NFPA surgery is age-related differences in tumor characteristics. Although the reasons for postoperative hematoma have not been clearly identified [42], a high risk of suprasellar hematoma formation exists when the tumor is adherent to the suprasellar neurovascular structures, particularly in recurrent cases with hard tumor consistency and/or a tendency to bleed. These factors make it difficult to remove the suprasellar tumor component using standard TSS. In fact, several of our elderly patients were switched to extended TSS for these reasons intraoperatively. However, extended TSS for elderly patients may increase the risk of postoperative CSF leakage, intracranial infection, and delayed chronic subdural hematoma formation [17, 43, 44]. Particularly in elderly patients, there is a surgical dilemma between the idea that sufficient decompression is a reasonable surgical goal and the risk of postoperative suprasellar hematoma. Martinez-Perez et al. [45] challenged what they viewed as a misleading claim by Tardivo et al. [38], who stated that “a partial resection of pituitary adenomas in the elderly population is preferred over a gross total one in order to reduce the surgical risk.” The authors also advocated that pituitary adenomas restricted to the sella should be completely removed independent of a patient’s age to prevent further symptomatic recurrence [45]. Although recurrence was sufficiently prevented in our series, complete resection of tumors confined to the sella may be important from another perspective to reduce the risk of postoperative suprasellar hematoma formation. Postoperative suprasellar hematoma is a catastrophic complication after TSS, with an incidence of 0.1–5.8%. It occurs occasionally after subtotal resection for large tumors with suprasellar extension and/or that present with pituitary apoplexy [23, 46–49]. Postoperative hematoma usually develops a few days postoperatively, and most patients experience deterioration of visual function and sometimes death [41]. Gondium et al. [6] reported a high rate of postoperative hematoma (n = 3; 5.4%) in their elderly group aged ≥ 70 years, whereas no hematomas were observed in the younger patient group. NFPAs may become hard and adhere to the suprasellar neurovascular structures in patients with a long disease duration. We argue that it is very difficult preoperatively to determine which patients should undergo invasive surgical treatment. Messerer et al. [50] advocated that early surgical intervention is desirable to achieve favorable visual outcomes and avoid complications because tumor size increases the risk of postoperative hematoma. Considering these issues, postoperative visual outcomes are likely to be poorer in the elderly, primarily because of delayed surgical intervention resulting from the complexities of concurrent ophthalmologic comorbidities. Furthermore, surgical difficulty increases and visual resiliency decreases in patients aged ≥ 75 years. In elderly patients, it is necessary to suspect the presence of a pituitary tumor and perform radiological examination when patients have non-specific findings on ophthalmologic testing, even with concurrent ophthalmologic comorbidities [51, 52]. It may be difficult to determine whether existing tumor compression is related to visual symptoms without the expertise of an experienced neurosurgeon. Conceivably, postoperative visual acuity may not improve as expected because of the effects of concurrent cataracts. However, it is important to perform pituitary surgery first to improve visual outcomes when there is evidence of pituitary tumor compression of the optic apparatus. As stated, Japan is a country with a long life expectancy, and the prevalence of cataracts and glaucoma varies greatly depending on age and region [53, 54]. Generally, the prevalence of cataracts, glaucoma, and age-related macular degeneration exponentially increases with age, and each of these conditions carries the risk of blindness [55, 56]. With the continued progression of population aging, the incidence of NFPAs in elderly individuals is expected to rise. In this population, visual impairment caused by NFPAs often goes unrecognized until the disease has reached an advanced stage. Ophthalmologists may encounter difficulties in identifying NFPA-related visual dysfunction, and neurosurgeons must be aware that postoperative visual recovery in elderly patients may be limited, even with appropriate surgical intervention. To improve visual outcomes after surgery, early diagnosis and timely treatment are imperative. Therefore, close collaboration between neurosurgeons and ophthalmologists is essential to ensure prompt detection and intervention. Study limitations This study had a retrospective design and was limited by the small sample size. Although several cases had a delayed diagnosis, there were also several cases in which patients diagnosed as having pituitary tumors declined surgical treatment for a time or were monitored over time because of their advanced age. In any case, delaying surgery—especially in elderly patients—may result in a missed opportunity to improve visual function postoperatively, even if the procedure itself does not worsen visual outcomes. Conclusions Several factors affect postoperative visual outcomes in elderly patients with NFPA. Because of the high prevalence of concomitant ophthalmic diseases in these patients, there is a possibility of delayed diagnosis and surgical intervention. Clinicians must consider the possibility that visual function may not improve as expected in such cases. Early surgical intervention after the onset of visual symptoms is desirable in elderly patients with NFPA, with particular care to avoid postoperative suprasellar hematoma. Abbreviations CSF cerebrospinal fluid NFPA non-functioning pituitary adenoma TSS transsphenoidal surgery Declarations Acknowledgments We thank Jane Charbonneau, DVM, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript. Competing Interests and Funding The authors declare no competing interests relevant to the content of this article. No specific funding was received for the present study. Ethics Approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not report animal studies. This study was approved by the ethics committee of the Kurume University School of Medicine (approval number: 18019). Informed Consent All participants agreed to the proposed treatment plan after all options for the management of non-functioning pituitary adenomas had been clearly explained. Informed consent was obtained from all participants. Consent to participate All patients provided written informed consent to participate in this study and agreed to both the proposed treatment plan and the analysis of their clinical data. Consent to publish All authors have read and approved the final manuscript. All patients described in this study approved the publication of this study. Data availability The datasets and data analyzed in the study will be made available by the corresponding author upon reasonable request. Author contributions Conceptualization: Kiyohiko Sakata, Aya Hashimoto, and Masatoshi Haruta. Methodology: Kiyohiko Sakata, Aya Hashimoto, and Sosho Kajiwara. Formal analysis and investigation: Yoshinori Hashimoto and Yusuke Otsu. Writing – original draft preparation: Kiyohiko Sakata. Writing – review and editing: Masatoshi Haruta and Motohiro Morioka. Supervision: Shigeo Yoshida and Motohiro Morioka. References Aflorei ED, Korbonits M (2014) Epidemiology and etiopathogenesis of pituitary adenomas. 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Minniti G, Esposito V, Piccirilli M, Fratticci A, Santoro A, Jaffrain-Rea ML (2005) Diagnosis and management of pituitary tumours in the elderly: a review based on personal experience and evidence of literature. Eur J Endocrinol 153:723-735. doi: 10.1530/eje.1.02030. Watanabe T, Uehara H, Takeishi G et al (2019) Characteristics of preoperative visual disturbance and visual outcome after endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary adenoma in elderly patients. World Neurosurg. 126:e706-712. doi: 10.1016/j.wneu.2019.02.132. Zhan R, Ma Z, Wang D, Li X (2015) Pure endoscopic endonasal transsphenoidal approach for nonfunctioning pituitary adenomas in the elderly: surgical outcomes and complications in 158 patients. World Neurosurg 84:1572-1578. doi. 10.1016/j.wneu.2015.08.035. Azab MA, O’Hagan M, Abou-Al-Shaar H, Karsy M, Guan J, Couldwell WT (2019) Safety and outcome of transsphenoidal pituitary adenoma resection in elderly patients. World Neurosurg 122:e1252-e1258. doi: 10.1016/j.wneu.2018.11.024. Hong J, Ding X, Lu Y (2008) Clinical analysis of 103 elderly patients with pituitary adenomas: transsphenoidal surgery and follow-up. J Clin neurosci 15:1091-1095. doi: 10.1016/j.jocn.2007.11.003. Jahangiri A, Lamborn KR, Blevins L, Kunwar S, Aghi MK (2012) Factors associated with delay to pituitary adenoma diagnosis in patients with visual loss. J Neurosurg 116:283-289. doi: 10.3171/2011.6.JNS101663. Liu J, Li C, Xiao Q et al (2015) Comparison of pituitary adenomas in elderly and younger adults: clinical characteristics, surgical outcomes, and prognosis. J Am Geriatr Soc 63:1924-1930. doi: 10.1111/jgs.13590. Garvayo M, Villa C, Jouinot A et al (2023) Pituitary surgery outcome in patients 75 years and older: a retrospective study. Acta Neurochir (Wien) 165:3409-3420. doi: 10.1007/s00701-023-05809-x Quah BL, Edwards-Bailey A, Gnanalingham K et al (2022) Endoscopic transsphenoidal surgery for biochemically and clinically non-functioning adenohypophyseal tumours in the elderly: experience from a single UK centre. Endocrine 75:872-882. doi: 10.1007/s12020-021-02910-y. Robenshtok E, Benbassat CA, Hirsch D (2014) Clinical course and outcome of nonfunctioning pituitary adenomas in the elderly compared with younger age groups. Endocr Pract 20:159-164. doi: 10.4158/EP13182.OR. Thakur JD, Corlin A, Mallari RJ et al (2021) Pituitary adenomas in older adults (≥65 years): 90-day outcomes and readmissions: a 10-year endoscopic endonasal surgical experience. Pituitary 24:14-26 doi: 10.1007/s11102-020-01081-9. Alexander TD, Chitguppi C, Collopy S et al (2022) Surgical outcomes of endoscopic transsphenoidal pituitary adenoma resection in elderly versus younger patients. J Neurol Surg B Skull Base 83:405-410. doi: 10.1055/a-1680-1572. Memel Z, Chesney K, Pamgal DJ, Bonney PA, Carmichael JD, Zada G et al (2019) Outcomes following transsphenoidal pituitary surgery in the elderly: a retrospective single-center review. Oper Neurosurg 16:302-309. doi: 10.1093/ons/opy109. Spina A, Losa M, Mortini P (2019) Pituitary adenomas in elderly patients: clinical and surgical outcome analysis in a large series. Endocrine 65:637-645. doi. 10.1007/s12020-019-01959-0. Wilson PJ, Omay SB, Kacker A, Anand VK, Schwartz (2018) Endonasal endoscopic pituitary surgery in the elderly. J Neurosurg 128:429-436. doi: 10.3171/2016.11.JNS162286. Fang Y, Pei Z, Chen H et al (2021) Diagnostic value of Knosp grade and modified Knosp grade for cavernous sinus invasion in pituitary adenomas: a systematic review and meta-analysis. Pituitary 24:457-464. doi: 10.1007/s11102-020-01122-3. Lang Y, Guo S, Tuo Y et al (2025) Immature PIT1-lineage pituitary neuroendocrine tumors/adenomas, a morphologically unique pituitary neuroendocrine tumors/adenomas commonly with cytologic atypia features and a prediction for aggressive clinical potential. Am J Surg pathol 49:243-250. doi: 10.1097/PAS. 0000000000002339. Ng S, Messerer M, Engelhardt J et al (2021) Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section. Acta Neurochir (Wien) 163: 3131-3142. doi: 10.1007/s00701-021-04953-6. Nishioka H (2023) Aggressive pituitary tumors (PitNETs). Endocr J 70:241-248. doi: 10.1507/endocrj.EJ23-0007. Portvedo S, Neto LV, Soares P, de Carvalho DP, Takiya CM, Miranda-Alves L (2022) Aggressive nonfunctioning pituitary neuroendocrine tumors. Brain Tumor Pathol 39:183-199. doi: 10.1007/s10014-022-00441-6. Strickland BA, Shahrestani S, Briggs RG et al (2021) Silent corticotroph pituitary adenomas: clinical characteristics, long-term outcomes, and management of disease recurrence. J Neurosurg 135:1706-1713. doi: 10.3171/2020.10.JNS203236. Esposito F, Dusick JR, Fatemi N, Kelly DF (2007) Graded repair of cranial base defects and cerebrospinal fluid in transsphenoidal surgery. Oper Neurosurg (Hagerstown) 60(4 Suppl 2):295-303; discussion 303-304. doi: 10.1227/01.NEU.0000255354.64077.66. Barzaghi LR, Medone M, Losa M, Bianchi S, Giovanelli M, Mortini P (2012) Prognostic factors of visual field improvement after trans-sphenoidal approach for pituitary macroadenomas: review of the literature and analysis by quantitative method. Neurosurg Rev 35:369-379. doi: 10.1007/s10143-011-0365-y. Butenschoen VM, Schwendinger N, von Werder A et al (2021) Visual acuity and its postoperative outcome after transsphenoidal adenoma resection. Neurosurg Rev 44:2245-2251. doi: 10.1007/s10143-020-01408-x. Lee S, Kim SJ, Yu YS et al (2013) Prognostic factors for visual recovery after transsphenoidal pituitary adenectomy. Br J Neurosurg 27:425-429. doi: 10.3109/02688697.2013.767316. Luomaranta T, Raappana A, Saarela V, Liinamaa MJ (2017) Factors affecting the visual outcome of pituitary adenoma patients treated with endoscopic transsphenoidal surgery. World Neurosurg 105 :422-431. doi: 10.1016/j.wneu.2017.05.144. Muskens IS, Najafabadi AHZ, Briceno V et al (2017) Visual outcomes after endoscopic endonasal pituitary adenoma resection: a systematic review and meta-analysis. Pituitary 20:539-552. doi: 10.1007/s11102-017-0815-9. Pelsma ICM, Verstegen MJT, de Vries F et al (2020) Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study. Pituitary 23:417-429. doi: 10.1007/s11102-020-01044-0. Tardivo V, Panner F, Garbossa D et al (2020) Surgical management of pituitary adenomas: does age matter? Pituitary 23:92-102. doi. 10.1007/211102-019-01014-1. Pereira EA, Plaha P, Chari A et al (2014) Transsphenoidal pituitary surgery in the elderly is safe and effective. Br J Neurosurg 28 :616-621. doi: 10.3109/02688697.2013.872225. Gerges MM, Arnaout MM, El Asri AC et al (2019) Increased frequency of cataract surgery in patients over age 50 with pituitary macroadenomas and chiasmal compression. Pituitary 22:405-410. doi: 10.1007/s11102-019-00970-y. Marzola P, Melzer T, Pavesi E, Gil-Mohapel J, Brocardo PS (2023) Exploring the role of neuroplasticity in development, aging, and neurogeneration. Brain Sci 13:1610. doi: 10.3390/brainsci13121610. Zhang Z, Li S, Wang Y (2024) Visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors: a retrospective cohort study. Acta Neurochir (Wien) 166:127. doi: 10.1007/s00701-024-06027-9. Kenning TJ, Pinheiro-Neto CD (2018) Complications of extended endoscopic endonasal surgery in elderly patients. J Neurol Surg B 79(suppl S3):S287-S-288. doi: 10.1055/s-0038-1625948. Takeuchi K, Watanabe T, Nagatani T, Nagata Y, Chu J, Wakabayashi T (2016) Incidence and risk factors of subdural hematoma after intraoperative cerebrospinal fluid leakage during the transsphenoidal approach. Pituitary 19:565-572. doi: 10.1007/s11102-016-0746-x. Martinez-Perez R, Carrau R, Prevedello DM (2020) Shall we be less aggressive in pituitary surgery in the elderly? Pituitary 23:745-747. doi: 10.1007/s11102-020-01030-6. Butterfield JT, Araki T, Guillaume D et al (2022) Estimating risk of pituitary apoplexy after resection of giant pituitary adenomas. J Neurol Surg B Skull Base 83(suppl S2):e152-e159. doi: 10.1055/s-0041-1722993. El-Asmar N, El-Sibai K, Al-Aridi R, Selman WR, Arafah BM (2016) Postoperative sellar hematoma after pituitary surgery: clinical and biochemical characteristics. Eur J Endocrinol 174:573-582. doi: 10.1530/EJE-15-0961. Osorio RC, Aabedi AA, Carson W et al (2023) Risk factors for significant postoperative hemorrhage after pituitary neuroendocrine tumor resection: a case-control study of 1066 surgeries. Neurosurg 93:206-214. doi: 10.1227/neu.0000000000002404. Younus I, Gerges MM, Saniya S et al (2020) Incidence and risk factors associated with reoperation for sellar hematoma following endoscopic transsphenoidal pituitary surgery. J Neurosurg 133:702-708. doi: 10.3171/2019.6.JNS191169. Messerer M, Dubourg J, Raverot G et al (2013) Non-functioning pituitary macro-incidentalomas benefit from early surgery before becoming symptomatic. Clin Neurol Neurosurg 115:2514-2520. doi: 10.1016/j.clineuro.2013.10.007. Hajiabadi M, Alimohamadi M, Fahlbusch R (2015) Decision making for patients with concomitant pituitary macroadenoma and ophthalmologic comorbidity: a clinical controversy. World Neurosurg 84:147-153. doi: 10.1016/j.wneu.2015.02.043. Nair SS, Varsha AS, Hegde A et al (2024) Correlation of pre-operative and post-operative retinal nerve fibre layer thickness with visual outcome following decompression of pituitary macroadenoma. Clin Neurol Neurosurg 244:108446. doi: 10.1016/j.clineuro.2024.108446. Hashemi H, Pakzad R, Yekta A (2020) Global and regional prevalence of age-related cataract: a comprehensive systematic review and meta-analysis. Eye 34:1357-1370 doi: 10.1038/s41433-020-0806-3. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY (2014) Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophtalmology 121:2081-2090. doi: 10.1016/j.ophtha.2014.05.013. Vision Loss Expert Group of the Global Burden of Disease Study; GBD 2019 Blindness and Vision Impairment Collaborators (2024) Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020. Eye (Lond) 38:2156-2172. doi: 10.1038/s41433-024-02961-1. GBD 2019 Blindness and Vision Impairment Collaborators; Vision Loss Expert Group of the Global Burden of Disease Study (2021) Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable sight: an analysis for the Global Burden of Disease Study. Lancet Glob Health 9:e144-e160. doi: 10.1016/S2214-109X(20)30489-7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7319844","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":502967409,"identity":"c256c797-6e06-4486-9e27-2c499b6dc519","order_by":0,"name":"Kiyohiko Sakata","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYBACCWYg8YGBgbGBB0WcB7tymBbGGaRpAWJmHkwteIBkO4/hY9scG9kGnjNmn3lzbBgMDjA//MAgcwenFmlmHmPj3G1pxg28PcazebelAbWwGUsw8DzDqUWOmcdMOnfb4cQGfh5jZt5th+s3HGAwA/rlMH4tltv+w7T8B9rC/g2vFmmQFsZtBxJBDgNqOQDUwoPfFslmtmLD3m3Jxm08x4oZ525LZpA8zFMskYDHLxLnD2988HObnWw/T/Jmhrfb7Bj4jrdv/PCxB3eIMTBwGIApNrgAKD0k9hzAo4X9ATbRH/i0jIJRMApGwQgDABxGSFsNY1IcAAAAAElFTkSuQmCC","orcid":"","institution":"Kurume University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Kiyohiko","middleName":"","lastName":"Sakata","suffix":""},{"id":502967410,"identity":"1052eaca-6c0a-4ca9-80c9-0c6cfe7bdff0","order_by":1,"name":"Aya Hashimoto","email":"","orcid":"","institution":"Kurume University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Aya","middleName":"","lastName":"Hashimoto","suffix":""},{"id":502967413,"identity":"faab3a7b-bcef-42e1-b2c1-9f2f57a22d76","order_by":2,"name":"Masatoshi Haruta","email":"","orcid":"","institution":"Kurume University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masatoshi","middleName":"","lastName":"Haruta","suffix":""},{"id":502967416,"identity":"51711aac-3aba-46d8-8474-3218fd9111b9","order_by":3,"name":"Yoshinori Hashimoto","email":"","orcid":"","institution":"Kurume University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yoshinori","middleName":"","lastName":"Hashimoto","suffix":""},{"id":502967417,"identity":"9f3c28f7-82b2-4585-85ed-349263240daa","order_by":4,"name":"Sosho Kajiwara","email":"","orcid":"","institution":"Kurume University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sosho","middleName":"","lastName":"Kajiwara","suffix":""},{"id":502967418,"identity":"dffa1018-b81d-4436-9783-d56dcf7ba72c","order_by":5,"name":"Yusuke Otsu","email":"","orcid":"","institution":"Kurume University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yusuke","middleName":"","lastName":"Otsu","suffix":""},{"id":502967419,"identity":"da91dafb-9fb4-4440-b2e0-2e97fa2c7b6b","order_by":6,"name":"Shigeo Yoshida","email":"","orcid":"","institution":"Kurume University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shigeo","middleName":"","lastName":"Yoshida","suffix":""},{"id":502967420,"identity":"33d372d4-9c1d-46cf-a741-80a0e0e27c0e","order_by":7,"name":"Motohiro Morioka","email":"","orcid":"","institution":"Kurume University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Motohiro","middleName":"","lastName":"Morioka","suffix":""}],"badges":[],"createdAt":"2025-08-07 14:38:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7319844/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7319844/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89564616,"identity":"2b4c493c-5eac-447b-bf59-1cb9106c79cb","added_by":"auto","created_at":"2025-08-21 10:37:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":5052278,"visible":true,"origin":"","legend":"\u003cp\u003eAn 81-year-old woman presented with progressive visual deterioration. She had undergone surgery for a non-functioning pituitary adenoma 30 years earlier.\u003c/p\u003e\n\u003cp\u003e(a) Recurrent tumors extending supra-medially from both cavernous sinuses were identified. (b, c) Fifteen hours after the first surgery, a suprasellar hematoma developed from a deep residual tumor and led to visual deterioration. (d) The hematoma and residual suprasellar tumors were removed by emergency reoperation, but deteriorated vision remained despite adequate decompression. Intraoperative findings showed the initial surgery (e, f) and subsequent emergency surgery (g, h) for this recurrent tumor; (e) the tumor was elastic, hard, and highly hemorrhagic, with a narrow space connecting the tumor to the suprasellar region (\u003cem\u003ewhite arrow\u003c/em\u003e) between bilateral cavernous tumors. (f) Decompression of the anterior visual pathway was confirmed after switching to extended endoscopic endonasal transsphenoidal surgery. (g) We removed the hemorrhagic hard tumor during emergency reoperation. (h) Complete relief of compression of the optic apparatus and preservation of the pituitary gland and stalk (\u003cem\u003eblack asterisk\u003c/em\u003e) were confirmed\u003c/p\u003e","description":"","filename":"ElderlyNFPAFigure1.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7319844/v1/74a6beb80bda44c8f5525013.jpg"},{"id":90297034,"identity":"6216b3e5-7803-463a-836d-a9a1be4341e7","added_by":"auto","created_at":"2025-09-01 08:25:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6459179,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7319844/v1/f3b14677-adc7-4a30-874f-cb9052ee6440.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Are visual outcomes satisfactory after endoscopic endonasal transsphenoidal surgery in elderly patients with non-functioning pituitary adenomas?","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePituitary adenomas are relatively common tumors with a reported prevalence of 14\u0026ndash;23% in various autopsy or radiologic studies, accounting for 5\u0026ndash;20% of all intracranial tumors [1\u0026ndash;4]. Elderly patients account for up to 14% of all patients diagnosed with pituitary tumors, with most lesions being non-functioning pituitary adenomas (NFPAs) [5]. Increased life expectancy in the general population is causing rapid growth in the number of elderly persons, and the number of those diagnosed with NFPAs could continue to rise [6].\u003c/p\u003e\u003cp\u003eThe number of elderly persons, defined by the World Health Organization as those\u0026thinsp;\u0026ge;\u0026thinsp;65 years of age, is projected to reach 2.2\u0026nbsp;billion globally by the late 2070s, surpassing the number of children (under age 18 years). Despite the fact that the estimated total population worldwide has been revised downward compared with previous estimates, the proportion of elderly persons is likely to grow rapidly, nearly doubling between 2024 and 2054, and could comprise one third or more in many developed countries by 2054 [7]. The Japan Federation of Gerontological Societies recommends a definition of \u0026ge;\u0026thinsp;75 years of age for \u0026ldquo;elderly\u0026rdquo; since 2017 because the general population in Japan is already considered elderly [8].\u003c/p\u003e\u003cp\u003eOverall, patients with NFPA present with visual acuity and field dysfunction at an incidence of 13.0\u0026ndash;60.8% [9]; visual dysfunction is the most frequent presentation in elderly patients, with an incidence of 60\u0026ndash;80% [10]. Therefore, the reason for surgery in patients with NFPA is improvement of visual function as a result of compression of the anterior visual pathways involving the optic chiasma and optic nerves [11, 12]. However, the diagnosis of NFPA in the elderly is usually delayed because visual symptoms may not be recognized and can be attributed to aging or concurrent ophthalmologic diseases [13\u0026ndash;16]. Recent studies have reported that endoscopic endonasal transsphenoidal surgery (TSS) for NFPA is well-tolerated and feasible in elderly patients [5, 12, 13, 17\u0026ndash;20]. However, some studies have shown higher complication rates in elderly versus non-elderly patients [6, 16, 21\u0026ndash;24]. Therefore, a decision to perform surgical intervention for elderly patients with NFPA should be supported by postoperative favorable visual outcomes. We retrospectively evaluated surgical and visual outcomes in elderly patients with NFPA, compared with outcomes in non-elderly patients.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eThis was a case\u0026ndash;control study examining the clinical characteristics and postoperative visual outcomes of elderly patients who underwent surgery for NFPA. The patients\u0026rsquo; clinical variables and surgical case details were compared between elderly patients and non-elderly patients to identify factors that may contribute to visual outcomes.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePatients and data collection and settings\u003c/h3\u003e\n\u003cp\u003eWe enrolled and analyzed the data of 130 consecutive patients with NFPA who were treated surgically in our institution from January 2010 to December 2024. Patients were identified from the clinical records of those with a diagnosis of pituitary adenoma on the basis of clinical history and presentation, imaging studies, and hormone workup. Patients with non-pituitary adenoma and functional pituitary adenoma pathologies were excluded. This study was approved by the Ethics Committee of the Kurume University School of Medicine (approval number: 18019), and the study was performed in accordance with the guidelines of the Declaration of Helsinki. All participants provided informed consent to undergo the proposed treatment after all options for the management of NFPA had been clearly explained, and all patients agreed to participate in the study.\u003c/p\u003e\u003cp\u003eThe overall cohort was divided into an elderly group (aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years) and a non-elderly group (aged\u0026thinsp;\u0026lt;\u0026thinsp;74 years). The latter was further divided into younger patients (aged\u0026thinsp;\u0026lt;\u0026thinsp;64 years) and pre-old patients (65\u0026ndash;74 years).\u003c/p\u003e\u003cp\u003eClinical and surgical variables collected from the patients\u0026rsquo; medical charts comprised age, proportion of men/women, preoperative visual symptoms, preoperative hypopituitarism, maximum tumor size, cavernous sinus invasion (Knosp grade 4) [25], surgical approach, history of previous pituitary surgery, pathological diagnosis, resection rate, and postoperative complications. The pathological diagnosis was divided into the aggressive variant (tumors formerly diagnosed as \u0026ldquo;atypical adenoma,\u0026rdquo; Crooke\u0026rsquo;s cell tumors, silent corticotroph tumors, and immature PIT-1 lineage tumors) and the common variant (gonadotroph tumors, other silent tumors, and null cell tumors) [26\u0026ndash;30]. Regarding the resection rate, gross total resection was defined as complete tumor disappearance on postoperative magnetic resonance imaging. Subtotal resection was defined as \u0026gt;\u0026thinsp;90% removal of the tumor on magnetic resonance imaging, and tumor resection of \u0026lt;\u0026thinsp;90% was defined as partial resection. Preoperative hypopituitarism was defined as a requisite status of pituitary replacement therapy with hydrocortisone and/or levothyroxine sodium hydrate owing to pituitary apoplexy, previous surgeries, and symptomatic hypopituitarism caused by tumor growth. Postoperative complications that occurred within 30 days after surgery were recorded, including cerebrospinal fluid (CSF) leakage requiring surgical repair, new cranial nerve deficit, postoperative infection, delayed massive epistaxis, postoperative symptomatic suprasellar hematoma, development of permanent arginine vasopressin deficiency, and new postoperative hypopituitarism requiring continuous administration of hydrocortisone and/or levothyroxine sodium hydrate.\u003c/p\u003e\u003cp\u003eIn patients with preoperative visual impairment, we investigated the severity before surgery (defined as severe if the visual acuity of either eye was \u0026le;\u0026thinsp;0.1), presence of ophthalmologic comorbidities, cataract surgery prior to pituitary tumor surgery, and disease duration (except for patients who were not clearly aware of the onset of the disease). Postoperative visual outcomes were simply classified into three categories; improved, unchanged, and deteriorated, on the basis of the results of ophthalmological examination performed before and 2 weeks after surgery. Cases in which visual function improvement was not achieved were reevaluated 3 or 6 months after surgery.\u003c/p\u003e\u003cp\u003eThe final decision on visual outcomes was based on the ophthalmologist\u0026rsquo;s judgment. The status of \u0026ldquo;improved\u0026rdquo; included any visual field improvement even if there was no clear improvement in visual acuity. If the patient reported no subjective improvement when the changes in the ophthalmological results were equivocal, the results were considered \u0026ldquo;unchanged.\u0026rdquo; If there was any deterioration in either visual acuity or visual field, the results were considered \u0026ldquo;worsened.\u0026rdquo;\u003c/p\u003e\u003cp\u003eWe also investigated long-term outcomes regarding postoperative tumor control in our surgical cases in which sufficient follow-up data were available after discharge. Planned radiotherapy, whether stereotactic radiosurgery or intensity-modulated radiotherapy, for residual tumors, especially in the cavernous sinus or invasive tumors, was defined as treatment administered within 6 months after surgery. Outcomes were classified by the three age groups and categorized as follows: (1) no tumor recurrence or regrowth, (2) wait and scan for tumor regrowth after incomplete resection (subtotal resection/partial resection), (3) wait and scan for tumor recurrence after gross total resection, (4) addition of radiotherapy for tumor recurrence or regrowth, (5) required surgery for tumor recurrence or regrowth, and (6) required surgery followed by radiotherapy.\u003c/p\u003e\n\u003ch3\u003eSurgical methods\u003c/h3\u003e\n\u003cp\u003eThe surgical approaches were classified into usual endoscopic endonasal TSS via the enlarged sellar turcica, transcranial surgery that included simultaneous combined surgery with TSS, and endoscopic endonasal extended TSS that required opening of the tuberculum sellae and planum sphenoidale for a suprasellar tumor component. Transcranial surgery and simultaneous combined surgery were performed for giant tumors with multilobular extension. Extended TSS was performed for tumors that extended into the subfrontal area along the planum sphenoidale or tumors that had coalesced with suprasellar neurovascular structures. Sellar floor reconstruction was performed gradually using consolidated methods on the basis of the degree of intraoperative CSF leakage using thigh fat and fascia, bone pieces from the nasal septum, and vascularized nasoseptal flaps [31]. Perioperatively, antiplatelet therapy and/or anticoagulant therapy were discontinued in all cases.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eNormally distributed data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (minimum\u0026ndash;maximum values). For categorical variables, groups were compared using Fisher\u0026rsquo;s exact test. For normally distributed continuous datasets, the groups were compared using Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test. Multivariate logistic regression analysis was performed using significant categorical variables to identify predictive factors for postoperative visual improvement. A \u003cem\u003ep\u003c/em\u003e value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant, and statistical analyses were performed using JMP Student Edition (SAS Institute Inc., Cary, NC, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eClinical presentation\u003c/h2\u003e\u003cp\u003eThe cohort included 22 elderly patients. The patients\u0026rsquo; background data were compared with those of the remaining 108 non-elderly patients (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no statistically significant differences between the groups in the proportions of men/women, maximum tumor diameter, cavernous sinus invasion, status of preoperative pituitary replacement therapy, history of previous pituitary surgery, pathological diagnosis, and resection rate. Notably, preoperative visual dysfunction was a chief complaint in most elderly patients, and the prevalence was significantly different compared with non-elderly patients. The only patient without visual impairment had a tumor that extended beyond the sphenoid sinus and filled the nasal cavity, which was treated surgically to relieve nasal obstruction. Extended TSS was selected significantly more often in the elderly than non-elderly group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021), and invasive surgical treatments were avoided, such as simultaneous combined surgeries. However, half of the cases in which extended TSS was selected were switched from standard TSS during surgery because with suprasellar tumors, it was difficult to dissect into the sellar space due to adhesions, even though the tumors were not particularly large.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of characteristics between elderly and non-elderly groups of patients with non-functioning pituitary adenomas\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eElderly group\u003c/p\u003e\u003cp\u003e(\u0026ge;\u0026thinsp;75)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-elderly group\u003c/p\u003e\u003cp\u003e (\u0026lt;\u0026thinsp;74)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of patients\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e108\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge at diagnosis, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\u003cp\u003e(range: 75\u0026ndash;85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/p\u003e\u003cp\u003e(range: 17\u0026ndash;74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex, male:female\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 : 11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57 : 51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.820\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePreoperative\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003evisual dysfunction\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e95.5%\u003c/p\u003e\u003cp\u003e(Yes: 21, No: 1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e 67.6%\u003c/p\u003e\u003cp\u003e(Yes: 73, No: 35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePreoperative pituitary dysfunction\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28.6%\u003c/p\u003e\u003cp\u003e(Yes: 6, No: 16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.3%\u003c/p\u003e\u003cp\u003e(Yes: 24, No: 84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.588\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMaximum tumor diameter, mm\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e\u003cp\u003e(range: 18\u0026ndash;65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e\u003cp\u003e(range: 11\u0026ndash;63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.265\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGiant adenoma\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(\u0026ge;\u0026thinsp;40 mm)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.2%\u003c/p\u003e \u003cp\u003e(Yes: 4, No: 18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.7%\u003c/p\u003e\u003cp\u003e(Yes: 18, No: 90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCavernous sinus invasion\u003c/b\u003e,\u003c/p\u003e\u003cp\u003e\u003cb\u003eKnosp grade\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGrade 0\u0026ndash;2: 13\u003c/p\u003e\u003cp\u003eGrade 3: 3\u003c/p\u003e\u003cp\u003eGrade 4: 6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGrade 0\u0026ndash;2: 68\u003c/p\u003e\u003cp\u003eGrade 3: 26\u003c/p\u003e\u003cp\u003eGrade 4: 14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.811\u003c/p\u003e\u003cp\u003e0.107\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePast history of pituitary surgery\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19.0%\u003c/p\u003e\u003cp\u003e(Yes: 4, No: 18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.7%\u003c/p\u003e\u003cp\u003e(Yes: 11, No: 97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.283\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePathological diagnosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCommon variant: 19\u003c/p\u003e\u003cp\u003eAggressive variant: 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCommon variant: 100\u003c/p\u003e\u003cp\u003eAggressive variant: 8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.396\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgical approach\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eeTSS: 16\u003c/p\u003e\u003cp\u003eExtended eTSS: 6\u003c/p\u003e\u003cp\u003eTCS or combined\u003c/p\u003e\u003cp\u003eTCS\u0026thinsp;+\u0026thinsp;eTSS: 0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eeTSS: 92\u003c/p\u003e\u003cp\u003eExtended eTSS: 9\u003c/p\u003e\u003cp\u003eTCS or combined\u003c/p\u003e\u003cp\u003eTCS\u0026thinsp;+\u0026thinsp;eTSS: 7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.208\u003c/p\u003e\u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtent of tumor resection\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGTR: 13\u003c/p\u003e\u003cp\u003eSTR: 6, PR: 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGTR: 78\u003c/p\u003e\u003cp\u003eSTR: 22, PR: 8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.307\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eSurgical complications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19.0% (Yes: 5, No: 17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.1% (Yes: 12, No: 96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.165\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNewly developed\u003c/p\u003e\u003cp\u003ehypopituitarism: 1\u003c/p\u003e\u003cp\u003eSevere meningitis: 1\u003c/p\u003e\u003cp\u003ePostoperative\u003c/p\u003e\u003cp\u003esuprasellar hematoma: 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNewly developed hypopituitarism*: 2\u003c/p\u003e\u003cp\u003eNewly developed pAVPD: 5\u003c/p\u003e\u003cp\u003eCSF leakage*: 4\u003c/p\u003e\u003cp\u003eDelayed epistaxis: 2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as n or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (range) unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eGroups were compared using Fisher\u0026rsquo;s exact test or the chi-square test, as appropriate.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eBoldface \u003cem\u003ep\u003c/em\u003e values are statistically significant.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e*One patient developed both CSF leakage and newly developed partial hypopituitarism.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eCSF: cerebrospinal fluid, eTSS: endoscopic transsphenoidal surgery, GTR: gross total resection, pAVPD: permanent arginine vasopressin deficiency, PR: partial resection, STR: subtotal resection, TCS: transcranial surgery.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePostoperative complications\u003c/h3\u003e\n\u003cp\u003eThe postoperative complications differed remarkably between the elderly and non-elderly groups. In non-elderly patients, newly developed hypopituitarism required oral replacement therapy in two patients, permanent arginine vasopressin deficiency occurred in five patients, postoperative CSF leakage required surgical repair in four patients, and delayed massive epistaxis occurred in two patients. In elderly patients, newly developed hypopituitarism occurred in one patient, severe meningitis that required intensive care occurred in one patient, and postoperative symptomatic suprasellar hematoma occurred in three patients. Among the three patients with postoperative hematoma (two of whom had recurrent adenomas), two required emergency reoperation the day after the initial surgery because of severe visual impairment; the remaining patient was treated conservatively. The patient who was treated conservatively developed transient bitemporal hemianopsia but recovered to the preoperative state. The two patients who underwent reoperation developed visual deterioration but recovered to better vision quality than that before reoperation. All of these patients returned to their previous lives without hormonal replacement therapy. There was no mortality within 30 days after surgery in either group. A representative case is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003ePostoperative visual outcomes and concurrent ophthalmologic comorbidities\u003c/h3\u003e\n\u003cp\u003eWhen we compared the clinical characteristics between the elderly and non-elderly groups in patients with preoperative visual dysfunction, there were significant differences in the severity of visual impairment before surgery, disease duration (especially\u0026thinsp;\u0026gt;\u0026thinsp;1 year), prevalence of ophthalmologic comorbidities, and history of previous cataract surgery (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Visual outcomes were significantly less favorable in elderly patients than in non-elderly patients (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Despite sufficient tumor decompression, 8 of the 10 patients who showed no changes in visual function after surgery had a longer disease duration of several years. Six patients had glaucoma and were undergoing long-term eye-drop treatment, and four did not recover their visual function after pituitary surgery. Among 13 patients who had a history of previous cataract surgery, 9 had undergone cataract surgery after the onset of NFPA-related symptoms and experienced an unexpected course after cataract surgery and progression of visual symptoms. These were complex factors that delayed the timing of pituitary surgery, although the maximum tumor size was \u0026gt;\u0026thinsp;30 mm in all patients. Furthermore, among elderly patients whose postoperative visual function was unchanged compared with preoperative function, none required additional ophthalmologic treatment, including cataract surgery, for further visual recovery after pituitary surgery.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDifferences in preoperative visual status, disease duration, ophthalmologic comorbidities, and visual outcomes, stratified by age\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eElderly group\u003c/p\u003e\u003cp\u003e(\u0026ge;\u0026thinsp;75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eNon-elderly group (\u0026lt;\u0026thinsp;74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-old (\u0026ge;\u0026thinsp;65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYounger (\u0026lt;\u0026thinsp;64)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eNumber of patients with visual symptoms\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eSex, male:female\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e 10 : 11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e 39 : 34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.805\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 : 12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29 : 22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.447\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003ePreoperative severe visual status*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eYes: 8\u003c/p\u003e\u003cp\u003eNo: 13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e Yes: 11 No: 62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.031\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eYes: 4 No: 18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes: 7 No: 44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.724\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eMedian disease duration**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e18 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e 8 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.259\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eDisease duration\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e\u0026gt;\u0026thinsp;1 year\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e57.1%\u003c/p\u003e\u003cp\u003e(Yes: 12, No: 9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e20.5% (Yes: 15, No: 58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.2% (Yes: 4, No: 18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21.6% (Yes: 11, No: 40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eOphthalmologic comorbidities\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e85.7%\u003c/p\u003e\u003cp\u003e(Yes: 18, No: 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e23.3% (Yes: 15, No: 58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50.0% (Yes: 11, No:11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.8% (Yes: 4, No: 47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003ePrevious cataract surgery\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(% after NFPA onset)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e 61.9%\u003c/p\u003e\u003cp\u003e(61.5% after onset)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e 8.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.2% (66.7% after onset)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003ePostoperative visual outcome\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eImproved: 47.6%\u003c/p\u003e\u003cp\u003eUnchanged: 42.9%\u003c/p\u003e\u003cp\u003eWorsened: 9.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e Improved: 90.4%\u003c/p\u003e\u003cp\u003eUnchanged: 8.2%\u003c/p\u003e\u003cp\u003eWorsened: 1.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eImproved: 91.0%\u003c/p\u003e\u003cp\u003eUnchanged: 4.5%\u003c/p\u003e\u003cp\u003eWorsened: 4.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eImproved: 90.2%\u003c/p\u003e\u003cp\u003eUnchanged: 9.8%\u003c/p\u003e\u003cp\u003eWorsened: 0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eData are presented as n unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eGroups were compared using Fisher\u0026rsquo;s exact test or the chi-square test, as appropriate.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eBoldface \u003cem\u003ep\u003c/em\u003e values are statistically significant.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Cases in which vision in either the left or right eye decreased to \u0026le;\u0026thinsp;0.1.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e**Excluding eight patients in whom disease onset was unclear because they were unaware of their visual impairment. These patients were considered to have a short disease duration for visual symptoms.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eNFPA: non-functioning pituitary adenoma.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWhen we compared differences between the younger group and the pre-old group, there were also statistically significant differences in the prevalence of ophthalmologic comorbidities and previous cataract surgery. However, favorable visual outcomes were achieved, with no statistically significant differences in disease duration and the severity of visual impairment before surgery between the two groups. In the pre-old group, cataracts were present in 8 of 11 patients with ophthalmologic comorbidities. Six had undergone cataract surgery before pituitary surgery (four underwent cataract surgery after NFPA-related symptom onset), and the median disease duration for these six patients was 10.5 months.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003ePredictive factors associated with postoperative visual improvement\u003c/h2\u003e\u003cp\u003eWe also investigated the data of 91 patients with preoperative visual impairment, except for 3 patients with deteriorated vision after surgery, to determine whether postoperative vision was improved or unchanged. Multivariate logistic regression analysis revealed that disease duration\u0026thinsp;\u0026gt;\u0026thinsp;1 year and age at presentation\u0026thinsp;\u0026ge;\u0026thinsp;75 years were independent predictors of postoperative visual improvement (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePostoperative long-term disease outcomes during follow-up, stratified by age\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eElderly\u003c/p\u003e\u003cp\u003e(\u0026ge;\u0026thinsp;75)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-old\u003c/p\u003e\u003cp\u003e(65\u0026ndash;74)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYounger\u003c/p\u003e\u003cp\u003e(\u0026lt;\u0026thinsp;64)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of treated patients\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e \u003cb\u003eEligibility*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e 36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e67\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e% residual (STR/PR) tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28.4%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e% Recurrent tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.5%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e% Knosp grade 4 tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.9%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e% Aggressive variant\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.0%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePlanned radiotherapy**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLong-term disease outcome\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNo tumor recurrence/regrowth\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWait and scan for regrowth\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWait and scan for recurrence\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRadiotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRequired surgery\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e 0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgery followed by radiotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedian follow-up period\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(range)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.5 months\u003c/p\u003e\u003cp\u003e(6\u0026ndash;93 months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62 months\u003c/p\u003e\u003cp\u003e(6\u0026ndash;160 months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60 months\u003c/p\u003e\u003cp\u003e(6\u0026ndash;169 months)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as n unless otherwise indicated.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Eligibility for long-term assessment was defined as patients who were followed up radiologically for \u0026gt;\u0026thinsp;6 months.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e**These patients received radiotherapy within 6 months after surgery.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eSTR: subtotal resection, PR: partial resection.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eLong-term disease control and further treatment\u003c/h2\u003e\u003cp\u003eOf the eligible patients who were followed for \u0026gt;\u0026thinsp;6 months, 123 patients were followed for a median of 60.0 months (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Despite the high rates of residual tumors, recurrent tumors, and aggressive variants in the elderly group, no cases required additional treatment. Furthermore, in the pre-old group, all patients could be followed conservatively after surgery during follow-up, except for one case with former \u0026ldquo;atypical adenoma\u0026rdquo; that recurred 3 years after surgery. This patient underwent extended TSS followed by radiotherapy. In the younger group, seven patients required additional radiotherapy for residual tumors inside the cavernous sinus or for widely invading residual tumors. One younger patient underwent surgery for early cystic recurrence after subtotal resection but had no evidence of disease\u0026thinsp;\u0026gt;\u0026thinsp;10 years after reoperation. Overall, 89.4% of the patients showed no recurrence.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 4. Multivariable logistic regression analysis of predictive factors for postoperative visual improvement\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eEntire cohort\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"595\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategorical variant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdds ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eAge at presentation \u0026lt; 75 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;6.439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.58\u0026ndash;28.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0093\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eDisease duration \u0026lt; 1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;9.329\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.49\u0026ndash;41.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eNon-severe visual impairment at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1.361\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.26\u0026ndash;6.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.7042\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cstrong\u003eElderly and pre-old patient groups\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"595\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategorical variant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdds ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eAge at presentation \u0026lt; 75 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp; 19.488\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.14\u0026ndash;541.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0061\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eDisease duration \u0026lt; 1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;6.596\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.01\u0026ndash;60.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.0483\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eAbsence of ophthalmological comorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;0.359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.02\u0026ndash;4.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.4051\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCI: confidence interval.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we showed that visual outcomes after endoscopic TSS surgery for NFPA in the elderly group were significantly poorer than those in the non-elderly group. This is an important result for clinicians. In NFPA patients presenting with visual dysfunction, 56.4\u0026ndash;90.0% reported improved vision postoperatively [9]. Additionally, previous studies of visual outcomes after endoscopic TSS revealed that favorable visual outcomes were affected by age, preoperative severity of the visual status, and disease duration [32\u0026ndash;37]. The visual recovery rate in elderly patients in these studies, most of which used a cut-off value of 65 or 70 years of age, was not significantly different compared with non-elderly patients and ranged from 78.5\u0026ndash;91.0% [5, 6, 11, 12, 16, 19, 20, 23]. However, the visual recovery rate in several studies was \u0026lt;\u0026thinsp;67% [17, 18, 38, 39], and a series reported by Pereira et al. [39] reported a rate of only 41.2% for visual improvement in 102 patients aged\u0026thinsp;\u0026ge;\u0026thinsp;70 years.\u003c/p\u003e\u003cp\u003eSeveral factors may account for the wide variability in visual outcomes following endoscopic TSS for NFPAs in elderly patients. One possible explanation is a delayed diagnosis of the NFPA or prolonged disease duration prior to surgical intervention. Given the high prevalence of cataracts in this age group, optic nerve atrophy secondary to an NFPA may be obscured by lens opacity, potentially resulting in delayed diagnosis [11]. Gerges et al. [40] reported that among patients aged\u0026thinsp;\u0026ge;\u0026thinsp;50 years with NFPAs and visual impairment, 18.0% had cataracts and 12.5% underwent cataract surgery, a rate significantly higher than the national prevalence of cataract surgery (5.1%). Consistent with these findings, a substantial proportion of patients in our cohort had undergone cataract surgery prior to pituitary surgery. It is plausible that visual impairment caused by an NFPA was initially misattributed to cataracts. Consequently, cataract surgery was performed, but the anticipated visual improvement was not achieved. A subsequent comprehensive ophthalmologic and neurologic evaluation ultimately led to the correct diagnosis of an NFPA. Furthermore, several patients in our cohort had previously been treated for glaucoma. The visual field constriction associated with glaucoma may have masked the characteristic bitemporal hemianopia and/or central scotoma caused by the NFPA, thereby complicating early detection. In patients with a delayed diagnosis, postoperative visual recovery is not guaranteed\u0026mdash;even with sufficient decompression of the optic apparatus\u0026mdash;and blindness may develop if surgery is not planned in a timely manner.\u003c/p\u003e\u003cp\u003eJahangiri et al. [15] found that symptom duration of \u0026le;\u0026thinsp;6 months was significantly associated with recovery to baseline visual function, whereas neither age at diagnosis nor symptom duration was a significant predictor of postoperative visual improvement. Notably, age was significantly associated with symptom duration. Butenschoen et al. [33] reported that the strongest predictor of improvement of visual acuity after transsphenoidal tumor resection was age, which was most likely correlated with longer disease duration and the high prevalence of ophthalmologic comorbidities. Thus, several researchers have referred to the correlation between long symptom duration and ophthalmologic comorbidities in elderly patients regarding postoperative visual outcomes [13\u0026ndash;16]. However, our study is the first to our knowledge to confirm the statistically significant relationship between these factors and postoperative visual outcomes using pre- and postoperative datasets. The results of the multivariate analysis also showed that not only symptom duration but also aging were independent factors associated with postoperative visual improvement, which may be related to reduced physiological plasticity in neural function recovery specific to elderly patients [41]. Barzaghi et al. [32] reported that preoperative visual impairment was more severe in cases with a disease duration of \u0026ge;\u0026thinsp;12 months and in patients aged\u0026thinsp;\u0026ge;\u0026thinsp;50 years. This finding suggests that younger patients are better able to compensate for microvascular deprivation due to tumor compression of small vessels that feed the chiasmatic crossing fibers from inferior aspects [32]. Notably, Wilson et al. [24] stated that elderly patients may be at increased risk of postoperative visual deterioration independent of surgical technique.\u003c/p\u003e\u003cp\u003eAnother reason for unfavorable visual outcomes in elderly patients after NFPA surgery is age-related differences in tumor characteristics. Although the reasons for postoperative hematoma have not been clearly identified [42], a high risk of suprasellar hematoma formation exists when the tumor is adherent to the suprasellar neurovascular structures, particularly in recurrent cases with hard tumor consistency and/or a tendency to bleed. These factors make it difficult to remove the suprasellar tumor component using standard TSS. In fact, several of our elderly patients were switched to extended TSS for these reasons intraoperatively. However, extended TSS for elderly patients may increase the risk of postoperative CSF leakage, intracranial infection, and delayed chronic subdural hematoma formation [17, 43, 44]. Particularly in elderly patients, there is a surgical dilemma between the idea that sufficient decompression is a reasonable surgical goal and the risk of postoperative suprasellar hematoma. Martinez-Perez et al. [45] challenged what they viewed as a misleading claim by Tardivo et al. [38], who stated that \u0026ldquo;a partial resection of pituitary adenomas in the elderly population is preferred over a gross total one in order to reduce the surgical risk.\u0026rdquo; The authors also advocated that pituitary adenomas restricted to the sella should be completely removed independent of a patient\u0026rsquo;s age to prevent further symptomatic recurrence [45]. Although recurrence was sufficiently prevented in our series, complete resection of tumors confined to the sella may be important from another perspective to reduce the risk of postoperative suprasellar hematoma formation.\u003c/p\u003e\u003cp\u003ePostoperative suprasellar hematoma is a catastrophic complication after TSS, with an incidence of 0.1\u0026ndash;5.8%. It occurs occasionally after subtotal resection for large tumors with suprasellar extension and/or that present with pituitary apoplexy [23, 46\u0026ndash;49]. Postoperative hematoma usually develops a few days postoperatively, and most patients experience deterioration of visual function and sometimes death [41]. Gondium et al. [6] reported a high rate of postoperative hematoma (n\u0026thinsp;=\u0026thinsp;3; 5.4%) in their elderly group aged\u0026thinsp;\u0026ge;\u0026thinsp;70 years, whereas no hematomas were observed in the younger patient group. NFPAs may become hard and adhere to the suprasellar neurovascular structures in patients with a long disease duration. We argue that it is very difficult preoperatively to determine which patients should undergo invasive surgical treatment. Messerer et al. [50] advocated that early surgical intervention is desirable to achieve favorable visual outcomes and avoid complications because tumor size increases the risk of postoperative hematoma.\u003c/p\u003e\u003cp\u003eConsidering these issues, postoperative visual outcomes are likely to be poorer in the elderly, primarily because of delayed surgical intervention resulting from the complexities of concurrent ophthalmologic comorbidities. Furthermore, surgical difficulty increases and visual resiliency decreases in patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years. In elderly patients, it is necessary to suspect the presence of a pituitary tumor and perform radiological examination when patients have non-specific findings on ophthalmologic testing, even with concurrent ophthalmologic comorbidities [51, 52]. It may be difficult to determine whether existing tumor compression is related to visual symptoms without the expertise of an experienced neurosurgeon. Conceivably, postoperative visual acuity may not improve as expected because of the effects of concurrent cataracts. However, it is important to perform pituitary surgery first to improve visual outcomes when there is evidence of pituitary tumor compression of the optic apparatus.\u003c/p\u003e\u003cp\u003eAs stated, Japan is a country with a long life expectancy, and the prevalence of cataracts and glaucoma varies greatly depending on age and region [53, 54]. Generally, the prevalence of cataracts, glaucoma, and age-related macular degeneration exponentially increases with age, and each of these conditions carries the risk of blindness [55, 56]. With the continued progression of population aging, the incidence of NFPAs in elderly individuals is expected to rise. In this population, visual impairment caused by NFPAs often goes unrecognized until the disease has reached an advanced stage. Ophthalmologists may encounter difficulties in identifying NFPA-related visual dysfunction, and neurosurgeons must be aware that postoperative visual recovery in elderly patients may be limited, even with appropriate surgical intervention. To improve visual outcomes after surgery, early diagnosis and timely treatment are imperative. Therefore, close collaboration between neurosurgeons and ophthalmologists is essential to ensure prompt detection and intervention.\u003c/p\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eStudy limitations\u003c/h2\u003e\u003cp\u003eThis study had a retrospective design and was limited by the small sample size. Although several cases had a delayed diagnosis, there were also several cases in which patients diagnosed as having pituitary tumors declined surgical treatment for a time or were monitored over time because of their advanced age. In any case, delaying surgery\u0026mdash;especially in elderly patients\u0026mdash;may result in a missed opportunity to improve visual function postoperatively, even if the procedure itself does not worsen visual outcomes.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSeveral factors affect postoperative visual outcomes in elderly patients with NFPA. Because of the high prevalence of concomitant ophthalmic diseases in these patients, there is a possibility of delayed diagnosis and surgical intervention. Clinicians must consider the possibility that visual function may not improve as expected in such cases. Early surgical intervention after the onset of visual symptoms is desirable in elderly patients with NFPA, with particular care to avoid postoperative suprasellar hematoma.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecerebrospinal fluid\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNFPA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003enon-functioning pituitary adenoma\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTSS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003etranssphenoidal surgery\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Jane Charbonneau, DVM, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests and Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests relevant to the content of this article. No specific funding was received for the present study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not report animal studies. This study was approved by the ethics committee of the Kurume University School of Medicine\u0026nbsp;(approval number: 18019).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants agreed to the proposed treatment plan after all options for the management of non-functioning pituitary adenomas had been clearly explained. Informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients provided written informed consent to participate in this study and agreed to both the proposed treatment plan and the analysis of their clinical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the final manuscript. All patients described in this study approved the publication of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets and data analyzed in the study will be made available by the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Kiyohiko Sakata, Aya Hashimoto, and Masatoshi Haruta.\u003c/p\u003e\n\u003cp\u003eMethodology: Kiyohiko Sakata,\u0026nbsp;Aya Hashimoto, and Sosho Kajiwara.\u003c/p\u003e\n\u003cp\u003eFormal analysis and investigation: Yoshinori Hashimoto and Yusuke Otsu.\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; original draft preparation: Kiyohiko Sakata.\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; review and editing: Masatoshi Haruta and Motohiro Morioka.\u003c/p\u003e\n\u003cp\u003eSupervision: Shigeo Yoshida and Motohiro Morioka.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAflorei ED, Korbonits M (2014) Epidemiology and etiopathogenesis of pituitary adenomas. 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Neurosurg Rev 35:369-379. doi: 10.1007/s10143-011-0365-y.\u003c/li\u003e\n\u003cli\u003eButenschoen VM, Schwendinger N, von Werder A et al (2021) Visual acuity and its postoperative outcome after transsphenoidal adenoma resection. Neurosurg Rev 44:2245-2251. doi: 10.1007/s10143-020-01408-x.\u003c/li\u003e\n\u003cli\u003eLee S, Kim SJ, Yu YS et al (2013) Prognostic factors for visual recovery after transsphenoidal pituitary adenectomy. Br J Neurosurg 27:425-429. doi: 10.3109/02688697.2013.767316.\u003c/li\u003e\n\u003cli\u003eLuomaranta T, Raappana A, Saarela V, Liinamaa MJ (2017) Factors affecting the visual outcome of pituitary adenoma patients treated with endoscopic transsphenoidal surgery. World Neurosurg 105 :422-431. doi: 10.1016/j.wneu.2017.05.144.\u003c/li\u003e\n\u003cli\u003eMuskens IS, Najafabadi AHZ, Briceno V et al (2017) Visual outcomes after endoscopic endonasal pituitary adenoma resection: a systematic review and meta-analysis. 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Clin Neurol Neurosurg 115:2514-2520. doi: 10.1016/j.clineuro.2013.10.007.\u003c/li\u003e\n\u003cli\u003eHajiabadi M, Alimohamadi M, Fahlbusch R (2015) Decision making for patients with concomitant pituitary macroadenoma and ophthalmologic comorbidity: a clinical controversy. World Neurosurg 84:147-153. doi: 10.1016/j.wneu.2015.02.043.\u003c/li\u003e\n\u003cli\u003eNair SS, Varsha AS, Hegde A et al (2024) Correlation of pre-operative and post-operative retinal nerve fibre layer thickness with visual outcome following decompression of pituitary macroadenoma. Clin Neurol Neurosurg 244:108446. doi: 10.1016/j.clineuro.2024.108446.\u003c/li\u003e\n\u003cli\u003eHashemi H, Pakzad R, Yekta A (2020) Global and regional prevalence of age-related cataract: a comprehensive systematic review and meta-analysis. Eye 34:1357-1370 doi: 10.1038/s41433-020-0806-3.\u003c/li\u003e\n\u003cli\u003eTham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY (2014) Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophtalmology 121:2081-2090. doi: 10.1016/j.ophtha.2014.05.013.\u003c/li\u003e\n\u003cli\u003eVision Loss Expert Group of the Global Burden of Disease Study; GBD 2019 Blindness and Vision Impairment Collaborators (2024) Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020. Eye (Lond) 38:2156-2172. doi: 10.1038/s41433-024-02961-1.\u003c/li\u003e\n\u003cli\u003eGBD 2019 Blindness and Vision Impairment Collaborators; Vision Loss Expert Group of the Global Burden of Disease Study (2021) Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable sight: an analysis for the Global Burden of Disease Study. Lancet Glob Health 9:e144-e160. doi: 10.1016/S2214-109X(20)30489-7.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"elderly patient, non-functioning pituitary adenoma, visual outcome, cataract, disease duration, postoperative suprasellar hematoma, transsphenoidal surgery","lastPublishedDoi":"10.21203/rs.3.rs-7319844/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7319844/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eNon-functioning pituitary adenomas (NFPA) in elderly patients may be followed conservatively because of a limited life expectancy, except when visual function is severely impaired. A decision to perform surgical intervention in these patients should be supported by favorable surgical and visual outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eData were analyzed for 130 patients with NFPA treated surgically since 2010. Patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years (elderly group) were compared with non-elderly patients aged\u0026thinsp;\u0026lt;\u0026thinsp;74 years regarding patient characteristics, tumor characteristics, surgical and visual outcomes, and preoperative visual function, including disease duration and ophthalmologic comorbidities.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eVisual impairment was highly prevalent in the 22 elderly patients with NFPA. However, postoperative visual improvement occurred in only 47.6% of these symptomatic patients, which was significantly poorer than that in non-elderly patients (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Furthermore, two of three patients who developed postoperative suprasellar hematoma after surgery experienced visual deterioration. In elderly patients, a high prevalence of ophthalmologic comorbidities and previous cataract surgery were associated with delayed surgery (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Additionally, patients aged 65\u0026ndash;74 years had a higher prevalence of ophthalmologic comorbidities and preceding cataract surgery than patients aged\u0026thinsp;\u0026lt;\u0026thinsp;64 years (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). However, favorable postoperative visual outcomes and disease duration were not statistically different between the two non-elderly groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eSeveral issues are associated with visual outcomes when performing surgery in elderly patients with NFPAs. Early surgical intervention after the onset of visual symptoms due to NFPA is desirable, and particular care is necessary to avoid postoperative suprasellar hematoma.\u003c/p\u003e","manuscriptTitle":"Are visual outcomes satisfactory after endoscopic endonasal transsphenoidal surgery in elderly patients with non-functioning pituitary adenomas?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-21 10:29:46","doi":"10.21203/rs.3.rs-7319844/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"68ab69a3-e83e-4159-bcb7-c1059ce2724c","owner":[],"postedDate":"August 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-01T08:24:18+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-21 10:29:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7319844","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7319844","identity":"rs-7319844","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}