Comparative real-world outcomes of treatment protocols for chronic pseudophakic cystoid macular oedema

Comparative real-world outcomes of treatment protocols for chronic pseudophakic cystoid macular oedema | 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 Comparative real-world outcomes of treatment protocols for chronic pseudophakic cystoid macular oedema Amber Khalil, Bence Tasnadi, Mostafa Khalil, Ahmed Hassane, Shohista Saidkasimova This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8429068/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 Pseudophakic cystoid macular oedema (pCMO) is a common complication following cataract surgery. Chronic pCMO is defined as oedema persisting for 90 days or longer postoperatively. No consensus currently exists regarding optimal management, resulting in considerable variability in clinical practice. This study aimed to evaluate current treatment approaches for chronic pCMO across Greater Glasgow area. Methods A retrospective cohort study was conducted on cases referred by community optometrists between January 2021 and December 2023 for post cataract surgery cystoid macular oedema (CMO). Inclusion criteria were OCT-confirmed oedema persisting for at least 90 days postoperatively. Exclusion criteria included postoperative CMO attributable to other causes, resolution within 90 days, or prior fovea involving diabetic macular oedema. Electronic health records and OCT images were reviewed to confirm diagnosis, collect demographic data, treatment regimens, duration, recurrence, and adverse effects of treatment. Results Thirty-four eyes from thirty-four patients were included in the study. The median time to resolution of chronic pCMO from diagnosis was 164 days. Median resolution times by treatment were as follows: exclusive topical therapy (ETT) 130 days; topicals plus intravitreal dexamethasone implant (TT-IDI) 177.5 days; topicals plus periocular triamcinolone acetonide (TT-PTA) 275 days; topicals plus intravitreal triamcinolone acetonide (TT-ITA) 123 days; and topicals plus intravitreal anti-VEGF (TT-AntiVEGF) 264 days. After escalation to adjuvant therapy, median resolution times were IDI 56.5 days; PTA 29 days; ITA 73 days; Anti-VEGF 124 days. Median time to escalation to adjuvant therapy was 108 days. Two patients experienced CMO recurrence at three and six months, respectively and one (2.9%) developed a steroid response. Conclusions Management of chronic pCMO varied substantially, with a median 108-day delay before escalation to invasive therapies, reflecting caution to escalate. Among adjuvant therapies, periocular triamcinolone and intravitreal dexamethasone demonstrated the most favourable resolution times, highlighting inflammation as the principal driver of chronic pCMO. In contrast, anti-VEGF therapy showed limited benefit. A median 40-day delay between referral and treatment initiation suggests potential for improved efficiency, particularly if initial topical therapy is commenced earlier by the referring optometrist. Earlier escalation to periocular or intravitreal corticosteroid therapy after 6-8 weeks of inadequate topical response may enhance outcomes. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Key Message Management of chronic pCMO requires a standardised escalation pathway beyond topical therapy. Earlier escalation to more invasive corticosteroid delivery (periocular triamcinolone or intravitreal triamcinolone/dexamethasone) speeds up resolution. Intravitreal anti-VEGF have a limited role in management of chronic pCMO. Introduction Pseudophakic cystoid macular oedema (pCMO), remains a significant cause of suboptimal visual recovery after uncomplicated cataract surgery [ 1 ]. While many cases resolve without intervention, a notable proportion persist beyond three months, defined as chronic pCMO [ 2 – 4 ]. These chronic cases are associated with enduring central visual impairment and reduced quality of life [ 2 – 4 ]. Optical coherence tomography is now the principal diagnostic and monitoring modality for macular fluid, providing sensitive and reproducible assessments [ 5 ]. The underlying pathophysiology of pCMO is predominantly inflammatory. Surgical trauma from phacoemulsification induces the release of prostaglandins and other mediators, disrupting the blood-retinal barriers and promoting intra-macular fluid accumulation [ 6 , 7 ]. Vascular endothelial growth factor (VEGF) may contribute to increased vascular permeability, though its role in pCMO is less pronounced than in diabetic or ischaemic macular oedema [ 8 ]. Mechanical factors such as epiretinal membrane formation or vitreomacular adhesion, can perpetuate chronicity in selected cases [ 9 ]. Several systemic and ocular factors, including diabetes mellitus, uveitis, retinal vein occlusion, and intraoperative posterior capsular rupture increase susceptibility to pCMO [ 10 ]. Incidence rates following uneventful phacoemulsification range from 0.1–2% but are higher among patients in these risk groups [ 11 ]. First line therapy typically involves topical corticosteroids and non-steroidal anti-inflammatory drugs (NASIDs) for postoperative pCMO [ 12 , 13 ]. However, evidence supporting their effectiveness for chronic or refractory pCMO is limited, and national consensus on the optimal duration of topical therapy prior to escalation is lacking [ 14 ]. Management following inadequate topical response includes several escalation strategies. Dexamethasone intravitreal implant are widely used due to their regulatory approval and sustained-release properties, though risks include endophthalmitis, implant migration, and steroid induced ocular hypertension [ 15 , 16 ]. Triamcinolone acetonide presents a lower risk, cost effective alternative, delivering posterior segment penetration and rapid anatomical improvement [ 15 , 17 , 18 ]. Nonetheless, it too carries a risk of increased intraocular pressure. In comparing intravitreal with periocular triamcinolone, both routes have shown significantly improved VA and reduced macular thickness, but intravitreal showed greater structural improvement whilst periocular route has lower risk of IOP elevation [ 19 ]. The role of intravitreal anti-vascular endothelial growth factor (anti-VEGF) in pCMO remains unclear. Although anti-VEGF agents are standard in macular oedema secondary to diabetic maculopathy and vein occlusion, pCMO is not primarily VEGF-driven and vitreous VEGF concentrations are typically not elevated in pseudophakic eyes without vascular comorbidities [ 13 ]. Existing studies tend to examine anti-VEGF therapy only after failure of corticosteroid intervention, complicating assessment of its true efficacy [ 20 ]. These factors limit the rationale for routine anti-VEGF use in pCMO outside of comorbid or steroid-intolerant eyes. Ongoing uncertainties include optimal timing for treatment escalation and comparative effectiveness of corticosteroid delivery routes. Real world evidence is needed to inform clinical practice and treatment sequencing. This study evaluates chronic pCMO management within Greater Glasgow and Clyde, comparing time to resolution, recurrence rates, and functional outcomes across commonly used treatment modalities. Methods A retrospective cohort study of patients with cystoid macular oedema following phacoemulsification cataract surgery were studied. Patients were identified from the NHS Greater Glasgow and Clyde cataract audit database from January 2021 to December 2023. Chronic pseudophakic cystoid macular oedema (pCMO) was defined as cystoid macular oedema identified on SD-OCT scans following cataract surgery persisting for 90 days or longer following diagnosis. Diagnosis was taken from the referral date once confirmed in clinic. Inclusion Criteria: (1) pCMO persisting 90 days or longer following cataract surgery. (2) Pre-operative CMO that resolved 90 days or longer prior to cataract surgery such as prior uveitis with CMO were also included. Exclusion criteria: (1) pCMO resolving within 90 days of diagnosis. (2) post-operative CMO attributable to alternative pathology such as diabetic macular oedema (3) Any prior history of centre involving diabetic macular oedema prior to surgery. Electronic healthcare records, and OCT images were reviewed for these patients. The following data were collected: sex, age at time of diagnosis of pCMO, date of diagnosis of pCMO, date of initiation of first-line treatment (topical corticosteroid and NSAID eye drops), date of initiation of second-line treatment (if applicable), choice of second-line treatment (periocular/intravitreal triamcinolone injection, intravitreal dexamethasone implant, or anti-VEGF intravitreal injection), time between first- and second-line option initiation, date of resolution of pCMO, time from diagnosis to resolution of pCMO, time from initiating final treatment option to resolution of pCMO, any recurrence of pCMO up to six months after resolution, past medical and ophthalmic history, and any adverse treatment effects. Microsoft Excel was used to analyse the data. This study was conducted in accordance with the Declaration of Helsinki. As a retrospective service evaluation using anonymised data, formal NHS Research Ethics Committee approval was not required. Informed consent was waived due to the retrospective nature of the study and use of anonymised data. There is no clinical trial number applicable to this work. The datasets generated and analysed during the current study are available from the corresponding author on reasonable request. Results Study Population and Demographics A search of the NHS Greater Glasgow and Clyde cataract audit database identified 42 patients with chronic cystoid macular oedema during the study period. Eight patients were excluded: seven due to a history of centre involving diabetic macular oedema (DMO) and one who had developed a branch retinal vein occlusion (BRVO) in the postoperative period. Consequently, 34 eyes from 34 patients met the inclusion criteria for chronic pCMO. The cohort consisted of 18 males (53%) with a median age at diagnosis of 73 years. Systemic comorbidities included hypertension in 15 patients (44%) and type 2 diabetes mellitus (T2DM) in eight patients (23.5%). Regarding ocular history, 22 eyes (65%) had no prior or coexisting comorbidities. Among those with ocular comorbidities, findings included: prior resolved uveitis without macular oedema (n=5, 14.7%); diabetic retinopathy without maculopathy (n=3, 8.8%); prior BRVO without macular oedema (n=3, 8.8%); and ocular hypertension (n=2, 5.9%). Treatment Timelines The mean time from referral to clinic review was 40 days. The mean time to initiate any treatment from the date of diagnosis was 15 days (range: 0-157 days). The median time from diagnosis to resolution of pCMO, was 164 days. Treatment Modalities and Subgroup Analysis Exclusive Topical Therapy (ETT) Twenty eyes (59%) were managed exclusively with topical corticosteroid and NSAID drops. In this group, the median time from diagnosis to resolution was 130 days, with a median treatment duration of 125 days to resolution. Adjuvant Therapies (Second Line) Fourteen eyes were escalated to second line therapy. Figure 1 compares the total time from diagnosis of chronic pCMO to resolution across all treatment modalities. Topical therapy plus Intravitreal Anti-VEGF Five eyes (15%) received anti-VEGF injections following initial topical therapy. Of these patients, two were treated with anti-VEGF due to previous history of BRVO resolved over 1 year prior to surgery, and one treated with anti-VEGF due to steroid response. The median time from diagnosis of chronic pCMO to resolution was 264 days. The median delay from initiating anti-VEGF therapy from topical therapy was 136 days (Figure 2). Following the switch, the median time to resolution was 124 days (Figure 3). Topical therapy plus Intravitreal Dexamethasone Implant (IDI) Six eyes (18%) received intravitreal dexamethasone implant following initial topical therapy. The median time to resolution from diagnosis of chronic pCMO was 177.5 days. The median delay to escalation was 10.5 days. Following IDI, the median time to resolution was 56.5 days. Topical therapy plus Periocular Triamcinolone Acetonide (PTA) Two eyes (6%) received periocular triamcinolone following initial topical therapy. The median time from diagnosis of chronic pCMO to resolution was 275 days. The median delay to escalation to PTA was 225 days. The median time to resolution of chronic pCMO following switch to PTA was 28 days. Topical therapy plus Intravitreal Triamcinolone Acetonide (ITA) One eye (3%) was treated with intravitreal triamcinolone following initial topical therapy. Escalation occurred after 42 days of topical therapy, with resolution achieved 73 days later (total 123 days from diagnosis of chronic pCMO to resolution). Visual and Anatomical Outcomes Across the study cohort, a median visual acuity improvement of 0.10 LogMAR was observed from diagnosis to resolution of chronic pCMO (Figure 4). Anatomically, the median reduction in central retinal thickness (CRT) on OCT was 155µm (figure 5). Safety Outcomes One patient (2.9%) developed a rise in intraocular pressure following prolonged exclusive topical therapy and was subsequently switched to intravitreal anti-VEGF therapy. The patients were followed up for 6 months following resolution of chronic pCMO. Recurrence was observed in two patients (5.9%). Both patients had a prior ocular history of BRVO and previously resolved parafoveal DMO, and they were initially managed with topical therapy with IDI and anti-VEGF respectively. Discussion With a prolonged reliance on topical medication and a delayed progression to invasive treatments, this real-world cohort study shows significant variance in the management of chronic pseudophakic cystoid macular oedema (pCMO). Our results demonstrate that earlier escalation to corticosteroid-based therapies resulted in significantly faster structural resolution, confirming the requirement for a planned and time-bound treatment pathway, even though topical therapy alone may heal chronic pCMO in some patients. The delay experienced at various levels of care is one of the study's main conclusions. One potentially modifiable factor contributing to chronicity is the median six-week gap between referral and clinic assessment, along with extra treatment initiation delays. This is especially important as decisions on escalation are frequently based on whether topical therapy is thought to be failing. The progression to second-line therapy is slowed when topical treatment is not started right away, which prolongs macular oedema and functional visual impairment. Increasing the accessibility of OCT imaging in community optometry settings offers a chance for early diagnosis and first-line treatment initiation before hospital review, which could reduce the length of the condition and improve results [ 21 ]. While more than half of the eyes eventually resolved with exclusive topical corticosteroid and NSAID therapy, this method was linked to the longest total time to resolution. A cautious approach to invasive procedures in ordinary practice is shown by the median delay of 108 days prior to advancement to second-line therapy. Although topical medication is frequently advised as the first line of treatment for postoperative CMO, there is still no data to support long-term use in chronic or refractory conditions [ 11 – 13 ]. According to our findings, topical medication is a suitable initial step, but if there is no improvement after four to six weeks, escalation should be initiated, in line with earlier guidelines [ 12 – 14 ]. Corticosteroid-based interventions were consistently linked to better results among second-line treatments. When compared to exclusive topical medication or anti-VEGF treatment, both intravitreal dexamethasone implant and periocular triamcinolone produced significantly shorter durations to resolution. Even though periocular triamcinolone is frequently administered late in the course of the disease, it produced exceptionally quick remission after escalation. According to accepted pathophysiological models [ 6 , 13 ], these results support inflammation as the primary cause of chronic pCMO. Periocular triamcinolone provides similar efficacy with lesser procedural risk, cheaper cost, and improved patient tolerability, but intravitreal dexamethasone implants are commonly employed because of its licensing and sustained-release characteristics [ 15 – 18 ]. Crucially, recurrence after periocular corticosteroid delivery should not be considered a therapy failure because recurrent injections can produce repeatable morphological improvement without the cumulative hazards of repeated intravitreal surgeries [ 17 , 18 ]. In contrast, intravitreal anti-VEGF therapy performed the worst in this cohort, showing little apparent improvement and a longer time to resolution. This finding is consistent with earlier research demonstrating that vitreous VEGF levels are not consistently raised in pseudophakic eyes and that VEGF is not a dominant mediator in pseudophakic CME in the absence of concurrent vascular disease [ 13 ]. The use of anti-VEGF therapy in pCMO has mostly been studied in refractory cases following corticosteroid failure, which complicates the interpretation of efficacy [ 20 , 22 , 23 ]. Restricting the treatment of anti-VEGF to patients with actual steroid intolerance or eyes with concurrent vascular disease is further supported by our real-world findings. Patients with systemic or ocular vascular comorbidities, such as diabetes mellitus or prior retinal vein occlusion, were more likely to experience a recurrence of pCMO. This is in line with earlier research showing that blood–retinal barrier malfunction and vascular comorbidities raise the risk of recurrent or persistent oedema after cataract surgery [ 2 , 3 ]. Thus, early detection of these higher-risk individuals and prompt therapy intensification may lower recurrence and enhance long-term results. With a median gain of 0.10 logMAR, this cohort's visual recovery was moderate despite notable structural improvement. This disparity between morphological and functional results has been documented in the past and may be the result of irreversible retinal remodelling linked to prolonged oedema [ 15 ]. These results highlight the significance of early and efficient treatment escalation to limit long-term retinal damage and maximise vision recovery. This study found a satisfactory safety profile. Only one patient ( 3%) experienced steroid-induced ocular hypertension, which is similar to or less common than that found in larger series (17%) [ 24 ]. Periocular administration offers a practical balance between efficacy and safety, especially in patients who need repeated treatment, whereas intravitreal corticosteroid delivery carries known hazards such as endophthalmitis and implant migration [ 25 , 26 ]. This study's retrospective approach, small sample size, and unequal distribution among treatment subgroups—which prevented a formal statistical comparison between modalities—are its main drawbacks. There was variation in escalation thresholds and time due to the clinician-dependent nature of treatment decisions. Visual acuity alone was used to measure functional results; patient-reported outcomes or quality of life were not formally evaluated. Nevertheless, this study finds practical ways to enhance the care of chronic pCMO and offers insightful real-world information about current NHS practice. Implications for practice These findings support a structured management algorithm in which chronic pCMO persisting beyond 6–8 weeks of topical therapy should trigger early escalation to corticosteroid injection, preferably periocular triamcinolone in the absence of contraindications. Anti-VEGF agents should be reserved for eyes with coexisting vascular pathology or true steroid intolerance. Future prospective trials are warranted to define optimal treatment duration, cost-effectiveness, and re-administration intervals to establish a standardised national pathway. Conclusion Through analysis of how chronic pCMO is currently managed across multiple ophthalmic centres, we have identified key areas for improvement in the management of chronic pCMO. Chronic pseudophakic cystoid macular oedema is predominantly an inflammatory process that often fails to resolve with topical therapy alone. Our real-world data show that while half of patients respond to prolonged topical treatment, earlier escalation to corticosteroid injection – either periocular triamcinolone or intravitreal dexamethasone achieves markedly faster resolution and improved anatomical outcomes. Periocular triamcinolone offers efficacy comparable to intravitreal dexamethasone, with a lower procedural risk and cost, supporting its use as a first-line escalation option in suitable patients. Anti-VEGF agents showed minimal benefit and should be reserved for eyes with coexisting vascular disease or steroid intolerance. The current delay from referral in the community to initiation of treatment in a tertiary referral centre represents suboptimal management. To optimise outcomes, pCMO management should adopt a structured, time-bound escalation pathway, with initiation of corticosteroid injection if no improvement is seen within six to eight weeks of topical therapy. Prospective trials are warranted to define optimal retreatment intervals and develop a standardised national protocol for chronic pCMO management. Declarations Conflicts of interest None. All authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors did not receive support from any organisation for the submitted work. Funding None. Author Contribution A.K & B.T contributed equally as joint first authors in this work. A.K & B.T wrote the main manuscript text. M.K and A.H were responsible for data collection and manuscript review. M.K was responsible for study design. S.S was responsible for final manuscript review. Data Availability The datasets generated and analysed during the current study are available from the corresponding author on reasonable request. References Grzybowski A et al (2016) Pseudophakic cystoid macular edema: update 2016. Clin Interv Aging 11:1221–1229. https://doi.org/10.2147/CIA.S111761 Henderson BA et al (2007) Clinical pseudophakic cystoid macular edema: risk factors and duration. J Cataract Refract Surg 33:1550–1558. https://doi.org/10.1016/j.jcrs.2007.05.013 Erikitola OO et al (2021) Persistent CME after uncomplicated cataract surgery: Scottish study. Eye (Lond) 35:584–591. https://doi.org/10.1038/s41433-020-0908-y Flach AJ (1998) Cystoid macular edema after cataract surgery: incidence and treatment. Trans Am Ophthalmol Soc 96:557–634 Benitah NR, Arroyo JG (2010) Pseudophakic cystoid macular edema. Int Ophthalmol Clin 50:139–153 Schaub F et al (2018) Preexisting epiretinal membrane and pseudophakic CME. Graefes Arch Clin Exp Ophthalmol 256:909–917. https://doi.org/10.1007/s00417-018-3954-4 Chu CJ et al (2016) Risk factors and incidence of macular edema after cataract surgery. Ophthalmology 123:316–323. https://doi.org/10.1016/j.ophtha.2015.10.001 Sivaprasad S et al (2005) NSAIDs for CME after cataract surgery: systematic review. Br J Ophthalmol 89:1420–1422. https://doi.org/10.1136/bjo.2005.073817 Kessel L et al (2014) Prevention of macular edema by steroid and NSAID drops. Ophthalmology 121:1915–1924. https://doi.org/10.1016/j.ophtha.2014.04.035 Heier JS et al (2000) Ketorolac vs prednisolone vs combination therapy for pseudophakic CME. Ophthalmology 107:2034–2038 Flach AJ et al (1987) Ketorolac 0.5% for chronic aphakic and pseudophakic CME. Am J Ophthalmol 103:479–486. https://doi.org/10.1016/s0002-9394(14)74268-0 Flach AJ et al (1991) Improvement in visual acuity in chronic pseudophakic CME with ketorolac. Am J Ophthalmol 112:514–519 Guo S et al (2015) Management of pseudophakic CME. Surv Ophthalmol 60:123–137. https://doi.org/10.1016/j.survophthal.2014.08.005 Conway MD et al (2003) Intravitreal triamcinolone for refractory CME. J Cataract Refract Surg 29:27–33. https://doi.org/10.1016/s0886-3350(02)01441-4 Mylonas G et al (2017) Dexamethasone implant vs triamcinolone for postoperative CME. Curr Eye Res 42:648–652. https://doi.org/10.1080/02713683.2016.1214968 Bellocq D et al (2015) Dexamethasone implants for post-surgical macular edema: EPISODIC study. Br J Ophthalmol 99:979–983. https://doi.org/10.1136/bjophthalmol-2014-306159 Benhamou N et al (2003) Intravitreal triamcinolone for refractory pseudophakic CME. Am J Ophthalmol 135:246–249. https://doi.org/10.1016/s0002-9394(02)01938-4 Konstantopoulos A et al (2007) Intravitreal triamcinolone for refractory CME: review. Eur J Ophthalmol 17:812–821 Choi YJ et al (2006) Intravitreal versus posterior subtenon injection of triamcinolone acetonide for diabetic macular edema. Korean J Ophthalmol 20:205–209. https://doi.org/10.3341/kjo.2006.20.4.205 Spitzer MS et al (2008) Bevacizumab for postoperative pseudophakic CME. J Cataract Refract Surg 34:70–75. https://doi.org/10.1016/j.jcrs.2007.08.021 Tasnadi B et al (2025) Lessons from a vitreoretinal virtual service in a tertiary center. Telemed J E Health 31:1236–1240. https://doi.org/10.1089/tmj.2025.0042 Arevalo JF et al (2009) Bevacizumab for refractory pseudophakic CME: PACORES results. Ophthalmology 116:1481–1487. https://doi.org/10.1016/j.ophtha.2009.04.006 Yilmaz T et al (2011) Systematic review: bevacizumab for pseudophakic CME. Clin Ophthalmol 5:923–929 Kersey JP, Broadway DC (2006) Corticosteroid-induced glaucoma: review. Eye (Lond) 20:407–416. https://doi.org/10.1038/sj.eye.6701895 Malclès A et al (2017) Safety of intravitreal dexamethasone implant (OZURDEX): SAFODEX study. Retina 37:1352–1359. https://doi.org/10.1097/IAE.0000000000001369 Khurana RN et al (2014) Dexamethasone implant migration: risk factors and management. Ophthalmology 121:67–71. https://doi.org/10.1016/j.ophtha.2013.06.033 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-8429068","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":565812692,"identity":"4e8d3986-a708-4364-9439-ef3aff67e976","order_by":0,"name":"Amber Khalil","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYFACHiCuYGAwYGBgZmZgsODhI07LGbgWCR42orQwtiG0MBDUwj/t7MHHlfPsos3Zex8bF9RIyLAxMD98dAOPFonbecmGZ7cl5+7sOW6cPOMYyGFsxsY5+Ky5nWMm2biNOXfDjTTmwzxsIC08bNL4tMjfzjH/2TinPnfD/WdALf+I0GIAtIWxseEw0BY25mTeNiK0GAL9Itlw7DjQL2nMxrx9QC3MBPwidzv34MeGmurc7ezHmKV5vtnY87M3P3yM1/uYgJk05aNgFIyCUTAKsAAA2A5BTzA35YQAAAAASUVORK5CYII=","orcid":"","institution":"Tennent Institute of Ophthalmology","correspondingAuthor":true,"prefix":"","firstName":"Amber","middleName":"","lastName":"Khalil","suffix":""},{"id":565812693,"identity":"ff62e550-4fe6-4f07-9127-b8d32f30522c","order_by":1,"name":"Bence Tasnadi","email":"","orcid":"","institution":"Tennent Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"Bence","middleName":"","lastName":"Tasnadi","suffix":""},{"id":565812694,"identity":"4b8e274c-67f8-46fc-afbb-e2f96dcce454","order_by":2,"name":"Mostafa Khalil","email":"","orcid":"","institution":"Tennent Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"Mostafa","middleName":"","lastName":"Khalil","suffix":""},{"id":565812695,"identity":"3a488ddf-2dc9-4ab1-8365-e70f7af0be1c","order_by":3,"name":"Ahmed Hassane","email":"","orcid":"","institution":"Tennent Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Hassane","suffix":""},{"id":565812696,"identity":"53ddc389-fb3d-4662-9870-b1ea970db647","order_by":4,"name":"Shohista Saidkasimova","email":"","orcid":"","institution":"Tennent Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"Shohista","middleName":"","lastName":"Saidkasimova","suffix":""}],"badges":[],"createdAt":"2025-12-23 01:38:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8429068/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8429068/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100362099,"identity":"5eddbd14-40d6-48ca-aa63-3f6c79e39f11","added_by":"auto","created_at":"2026-01-16 07:46:11","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":62867,"visible":true,"origin":"","legend":"\u003cp\u003eBox-and-whisker plot comparing time from diagnosis (in days) of pCMO, to resolution of pCMO across the treatment modalities. Horizontal line and adjacent number represent the median; X represents the mean; borders of grey box represent the interquartile range( IQR) (25\u003csup\u003eth\u003c/sup\u003e-75\u003csup\u003eth\u003c/sup\u003e percentile) and whiskers represent the most extreme data points within 1.5 x IQR.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8429068/v1/57b7012359e22204454f8260.jpg"},{"id":100361900,"identity":"cf42fc37-c7cb-4f8a-9b75-78c62f7d948d","added_by":"auto","created_at":"2026-01-16 07:45:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":57626,"visible":true,"origin":"","legend":"\u003cp\u003eBox-and-whisker plot comparing time taken in days to switch from initial topical therapy to the second-line (final) treatment modality, grouped by final treatment modality. Horizontal line and adjacent number represent the median; X represents the mean; borders of grey box represent the interquartile range( IQR) (25\u003csup\u003eth\u003c/sup\u003e-75\u003csup\u003eth\u003c/sup\u003e percentile) and whiskers represent the most extreme data points within 1.5 x IQR.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8429068/v1/4ed9a93bc18a2f4ecef20a88.jpg"},{"id":100013088,"identity":"5d69984a-d011-4369-bbde-3a8dcf8263d7","added_by":"auto","created_at":"2026-01-12 06:18:16","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":45979,"visible":true,"origin":"","legend":"\u003cp\u003eBox-and-whisker plot comparing time in days from having commenced the final treatment modality to resolution of pCMO. Horizontal line and adjacent number represent the median; X represents the mean; borders of grey box represent the interquartile range( IQR) (25\u003csup\u003eth\u003c/sup\u003e-75\u003csup\u003eth\u003c/sup\u003e percentile) and whiskers represent the most extreme data points within 1.5 x IQR.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8429068/v1/c39695ee347d0f04340e1cbd.jpg"},{"id":100013084,"identity":"e1b7c1b7-a30c-4408-b713-8bdb810ae4f5","added_by":"auto","created_at":"2026-01-12 06:18:16","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":43322,"visible":true,"origin":"","legend":"\u003cp\u003eBox-and-whisker plot comparing visual acuity in logMAR at diagnosis of pCMO and at resolution of pCMO. Horizontal line and adjacent number represent the median; X represents the mean; borders of grey box represent the interquartile range( IQR) (25\u003csup\u003eth\u003c/sup\u003e-75\u003csup\u003eth\u003c/sup\u003e percentile) and whiskers represent the most extreme data points within 1.5 x IQR.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8429068/v1/1291201c292ab8571a7d0681.jpg"},{"id":100013087,"identity":"c3497769-c830-4134-b720-e9cebc35b00d","added_by":"auto","created_at":"2026-01-12 06:18:16","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":38128,"visible":true,"origin":"","legend":"\u003cp\u003eBox-and-whisker plot comparing CRT at diagnosis of pCMO and at resolution of pCMO. Horizontal line and adjacent number represent the median; X represents the mean; borders of grey box represent the interquartile range( IQR) (25\u003csup\u003eth\u003c/sup\u003e-75\u003csup\u003eth\u003c/sup\u003e percentile) and whiskers represent the most extreme data points within 1.5 x IQR.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8429068/v1/8995fea65c9fae9437e29911.jpg"},{"id":100380850,"identity":"fd8bcbce-c5bf-43d9-8c35-0c3627a19899","added_by":"auto","created_at":"2026-01-16 10:35:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":729025,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8429068/v1/a337d4d5-f61e-4e6b-be67-737a1e891d69.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative real-world outcomes of treatment protocols for chronic pseudophakic cystoid macular oedema","fulltext":[{"header":"Key Message","content":"\u003col\u003e\n \u003cli\u003eManagement of chronic pCMO requires a standardised escalation pathway beyond topical therapy.\u003c/li\u003e\n \u003cli\u003eEarlier escalation to more invasive corticosteroid delivery (periocular triamcinolone or intravitreal triamcinolone/dexamethasone) speeds up resolution.\u003c/li\u003e\n \u003cli\u003eIntravitreal anti-VEGF have a limited role in management of chronic pCMO.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Introduction","content":"\u003cp\u003ePseudophakic cystoid macular oedema (pCMO), remains a significant cause of suboptimal visual recovery after uncomplicated cataract surgery [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. While many cases resolve without intervention, a notable proportion persist beyond three months, defined as chronic pCMO [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These chronic cases are associated with enduring central visual impairment and reduced quality of life [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Optical coherence tomography is now the principal diagnostic and monitoring modality for macular fluid, providing sensitive and reproducible assessments [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe underlying pathophysiology of pCMO is predominantly inflammatory. Surgical trauma from phacoemulsification induces the release of prostaglandins and other mediators, disrupting the blood-retinal barriers and promoting intra-macular fluid accumulation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Vascular endothelial growth factor (VEGF) may contribute to increased vascular permeability, though its role in pCMO is less pronounced than in diabetic or ischaemic macular oedema [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Mechanical factors such as epiretinal membrane formation or vitreomacular adhesion, can perpetuate chronicity in selected cases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral systemic and ocular factors, including diabetes mellitus, uveitis, retinal vein occlusion, and intraoperative posterior capsular rupture increase susceptibility to pCMO [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Incidence rates following uneventful phacoemulsification range from 0.1\u0026ndash;2% but are higher among patients in these risk groups [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFirst line therapy typically involves topical corticosteroids and non-steroidal anti-inflammatory drugs (NASIDs) for postoperative pCMO [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, evidence supporting their effectiveness for chronic or refractory pCMO is limited, and national consensus on the optimal duration of topical therapy prior to escalation is lacking [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eManagement following inadequate topical response includes several escalation strategies. Dexamethasone intravitreal implant are widely used due to their regulatory approval and sustained-release properties, though risks include endophthalmitis, implant migration, and steroid induced ocular hypertension [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Triamcinolone acetonide presents a lower risk, cost effective alternative, delivering posterior segment penetration and rapid anatomical improvement [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Nonetheless, it too carries a risk of increased intraocular pressure. In comparing intravitreal with periocular triamcinolone, both routes have shown significantly improved VA and reduced macular thickness, but intravitreal showed greater structural improvement whilst periocular route has lower risk of IOP elevation [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe role of intravitreal anti-vascular endothelial growth factor (anti-VEGF) in pCMO remains unclear. Although anti-VEGF agents are standard in macular oedema secondary to diabetic maculopathy and vein occlusion, pCMO is not primarily VEGF-driven and vitreous VEGF concentrations are typically not elevated in pseudophakic eyes without vascular comorbidities [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Existing studies tend to examine anti-VEGF therapy only after failure of corticosteroid intervention, complicating assessment of its true efficacy [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These factors limit the rationale for routine anti-VEGF use in pCMO outside of comorbid or steroid-intolerant eyes.\u003c/p\u003e \u003cp\u003eOngoing uncertainties include optimal timing for treatment escalation and comparative effectiveness of corticosteroid delivery routes. Real world evidence is needed to inform clinical practice and treatment sequencing. This study evaluates chronic pCMO management within Greater Glasgow and Clyde, comparing time to resolution, recurrence rates, and functional outcomes across commonly used treatment modalities.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA retrospective cohort study of patients with cystoid macular oedema following phacoemulsification cataract surgery were studied. Patients were identified from the NHS Greater Glasgow and Clyde cataract audit database from January 2021 to December 2023. Chronic pseudophakic cystoid macular oedema (pCMO) was defined as cystoid macular oedema identified on SD-OCT scans following cataract surgery persisting for 90 days or longer following diagnosis. Diagnosis was taken from the referral date once confirmed in clinic. Inclusion Criteria: (1) pCMO persisting 90 days or longer following cataract surgery. (2) Pre-operative CMO that resolved 90 days or longer prior to cataract surgery such as prior uveitis with CMO were also included. Exclusion criteria: (1) pCMO resolving within 90 days of diagnosis. (2) post-operative CMO attributable to alternative pathology such as diabetic macular oedema (3) Any prior history of centre involving diabetic macular oedema prior to surgery. Electronic healthcare records, and OCT images were reviewed for these patients.\u003c/p\u003e \u003cp\u003eThe following data were collected: sex, age at time of diagnosis of pCMO, date of diagnosis of pCMO, date of initiation of first-line treatment (topical corticosteroid and NSAID eye drops), date of initiation of second-line treatment (if applicable), choice of second-line treatment (periocular/intravitreal triamcinolone injection, intravitreal dexamethasone implant, or anti-VEGF intravitreal injection), time between first- and second-line option initiation, date of resolution of pCMO, time from diagnosis to resolution of pCMO, time from initiating final treatment option to resolution of pCMO, any recurrence of pCMO up to six months after resolution, past medical and ophthalmic history, and any adverse treatment effects. Microsoft Excel was used to analyse the data.\u003c/p\u003e \u003cp\u003e This study was conducted in accordance with the Declaration of Helsinki. As a retrospective service evaluation using anonymised data, formal NHS Research Ethics Committee approval was not required. Informed consent was waived due to the retrospective nature of the study and use of anonymised data. There is no clinical trial number applicable to this work. The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy Population and Demographics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA search of the NHS Greater Glasgow and Clyde cataract audit database identified 42 patients with chronic cystoid macular oedema during the study period. Eight patients were excluded: seven due to a history of centre involving diabetic macular oedema (DMO) and one who had developed a branch retinal vein occlusion (BRVO) in the postoperative period. Consequently, 34 eyes from 34 patients met the inclusion criteria for chronic pCMO.\u003c/p\u003e\n\u003cp\u003eThe cohort consisted of 18 males (53%) with a median age at diagnosis of 73 years. Systemic comorbidities included hypertension in 15 patients (44%) and type 2 diabetes mellitus (T2DM) in eight patients (23.5%). Regarding ocular history, 22 eyes (65%) had no prior or coexisting comorbidities. Among those with ocular comorbidities, findings included: prior resolved uveitis without macular oedema (n=5, 14.7%); diabetic retinopathy without maculopathy (n=3, 8.8%); prior BRVO without macular oedema (n=3, 8.8%); and ocular hypertension (n=2, 5.9%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment Timelines\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean time from referral to clinic review was 40 days. The mean time to initiate any treatment from the date of diagnosis was 15 days (range: 0-157 days). The median time from diagnosis to resolution of pCMO, was 164 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment Modalities and Subgroup Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eExclusive Topical Therapy (ETT)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTwenty eyes (59%) were managed exclusively with topical corticosteroid and NSAID drops. In this group, the median time from diagnosis to resolution was 130 days, with a median treatment duration of 125 days to resolution.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAdjuvant Therapies (Second Line)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFourteen eyes were escalated to second line therapy. Figure 1 compares the total time from diagnosis of chronic pCMO to resolution across all treatment modalities.\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eTopical therapy plus Intravitreal Anti-VEGF\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eFive eyes (15%) received anti-VEGF injections following initial topical therapy. Of these patients, two were treated with anti-VEGF due to previous history of BRVO resolved over 1 year prior to surgery, and one treated with anti-VEGF due to steroid response. The median time from diagnosis of chronic pCMO to resolution was 264 days. The median delay from initiating anti-VEGF therapy from topical therapy was 136 days (Figure 2). Following the switch, the median time to resolution was 124 days (Figure 3).\u003c/p\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003eTopical therapy plus Intravitreal Dexamethasone Implant (IDI)\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eSix eyes (18%) received intravitreal dexamethasone implant following initial topical therapy. The median time to resolution from diagnosis of chronic pCMO was 177.5 days. The median delay to escalation was 10.5 days. Following IDI, the median time to resolution was 56.5 days.\u0026nbsp;\u003c/p\u003e\n\u003col start=\"3\"\u003e\n \u003cli\u003eTopical therapy plus Periocular Triamcinolone Acetonide (PTA)\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTwo eyes (6%) received periocular triamcinolone following initial topical therapy. The median time from diagnosis of chronic pCMO to resolution was 275 days. The median delay to escalation to PTA was 225 days. The median time to resolution of chronic pCMO following switch to PTA was 28 days.\u0026nbsp;\u003c/p\u003e\n\u003col start=\"4\"\u003e\n \u003cli\u003eTopical therapy plus Intravitreal Triamcinolone Acetonide (ITA)\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eOne eye (3%) was treated with intravitreal triamcinolone following initial topical therapy. Escalation occurred after 42 days of topical therapy, with resolution achieved 73 days later (total 123 days from diagnosis of chronic pCMO to resolution).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisual and Anatomical Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcross the study cohort, a median visual acuity improvement of 0.10 LogMAR was observed from diagnosis to resolution of chronic pCMO (Figure 4). Anatomically, the median reduction in central retinal thickness (CRT) on OCT was 155µm (figure 5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne patient (2.9%) developed a rise in intraocular pressure following prolonged exclusive topical therapy and was subsequently switched to intravitreal anti-VEGF therapy. The patients were followed up for 6 months following resolution of chronic pCMO. Recurrence was observed in two patients (5.9%). Both patients had a prior ocular history of BRVO and previously resolved parafoveal DMO, and they were initially managed with topical therapy with IDI and anti-VEGF respectively.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWith a prolonged reliance on topical medication and a delayed progression to invasive treatments, this real-world cohort study shows significant variance in the management of chronic pseudophakic cystoid macular oedema (pCMO). Our results demonstrate that earlier escalation to corticosteroid-based therapies resulted in significantly faster structural resolution, confirming the requirement for a planned and time-bound treatment pathway, even though topical therapy alone may heal chronic pCMO in some patients.\u003c/p\u003e \u003cp\u003eThe delay experienced at various levels of care is one of the study's main conclusions. One potentially modifiable factor contributing to chronicity is the median six-week gap between referral and clinic assessment, along with extra treatment initiation delays. This is especially important as decisions on escalation are frequently based on whether topical therapy is thought to be failing. The progression to second-line therapy is slowed when topical treatment is not started right away, which prolongs macular oedema and functional visual impairment. Increasing the accessibility of OCT imaging in community optometry settings offers a chance for early diagnosis and first-line treatment initiation before hospital review, which could reduce the length of the condition and improve results [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile more than half of the eyes eventually resolved with exclusive topical corticosteroid and NSAID therapy, this method was linked to the longest total time to resolution. A cautious approach to invasive procedures in ordinary practice is shown by the median delay of 108 days prior to advancement to second-line therapy. Although topical medication is frequently advised as the first line of treatment for postoperative CMO, there is still no data to support long-term use in chronic or refractory conditions [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. According to our findings, topical medication is a suitable initial step, but if there is no improvement after four to six weeks, escalation should be initiated, in line with earlier guidelines [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCorticosteroid-based interventions were consistently linked to better results among second-line treatments. When compared to exclusive topical medication or anti-VEGF treatment, both intravitreal dexamethasone implant and periocular triamcinolone produced significantly shorter durations to resolution. Even though periocular triamcinolone is frequently administered late in the course of the disease, it produced exceptionally quick remission after escalation. According to accepted pathophysiological models [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], these results support inflammation as the primary cause of chronic pCMO. Periocular triamcinolone provides similar efficacy with lesser procedural risk, cheaper cost, and improved patient tolerability, but intravitreal dexamethasone implants are commonly employed because of its licensing and sustained-release characteristics [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Crucially, recurrence after periocular corticosteroid delivery should not be considered a therapy failure because recurrent injections can produce repeatable morphological improvement without the cumulative hazards of repeated intravitreal surgeries [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrast, intravitreal anti-VEGF therapy performed the worst in this cohort, showing little apparent improvement and a longer time to resolution. This finding is consistent with earlier research demonstrating that vitreous VEGF levels are not consistently raised in pseudophakic eyes and that VEGF is not a dominant mediator in pseudophakic CME in the absence of concurrent vascular disease [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The use of anti-VEGF therapy in pCMO has mostly been studied in refractory cases following corticosteroid failure, which complicates the interpretation of efficacy [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Restricting the treatment of anti-VEGF to patients with actual steroid intolerance or eyes with concurrent vascular disease is further supported by our real-world findings.\u003c/p\u003e \u003cp\u003ePatients with systemic or ocular vascular comorbidities, such as diabetes mellitus or prior retinal vein occlusion, were more likely to experience a recurrence of pCMO. This is in line with earlier research showing that blood\u0026ndash;retinal barrier malfunction and vascular comorbidities raise the risk of recurrent or persistent oedema after cataract surgery [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Thus, early detection of these higher-risk individuals and prompt therapy intensification may lower recurrence and enhance long-term results.\u003c/p\u003e \u003cp\u003eWith a median gain of 0.10 logMAR, this cohort's visual recovery was moderate despite notable structural improvement. This disparity between morphological and functional results has been documented in the past and may be the result of irreversible retinal remodelling linked to prolonged oedema [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These results highlight the significance of early and efficient treatment escalation to limit long-term retinal damage and maximise vision recovery.\u003c/p\u003e \u003cp\u003eThis study found a satisfactory safety profile. Only one patient ( 3%) experienced steroid-induced ocular hypertension, which is similar to or less common than that found in larger series (17%) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Periocular administration offers a practical balance between efficacy and safety, especially in patients who need repeated treatment, whereas intravitreal corticosteroid delivery carries known hazards such as endophthalmitis and implant migration [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study's retrospective approach, small sample size, and unequal distribution among treatment subgroups\u0026mdash;which prevented a formal statistical comparison between modalities\u0026mdash;are its main drawbacks. There was variation in escalation thresholds and time due to the clinician-dependent nature of treatment decisions. Visual acuity alone was used to measure functional results; patient-reported outcomes or quality of life were not formally evaluated. Nevertheless, this study finds practical ways to enhance the care of chronic pCMO and offers insightful real-world information about current NHS practice.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eImplications for practice\u003c/h2\u003e \u003cp\u003eThese findings support a structured management algorithm in which chronic pCMO persisting beyond 6\u0026ndash;8 weeks of topical therapy should trigger early escalation to corticosteroid injection, preferably periocular triamcinolone in the absence of contraindications. Anti-VEGF agents should be reserved for eyes with coexisting vascular pathology or true steroid intolerance. Future prospective trials are warranted to define optimal treatment duration, cost-effectiveness, and re-administration intervals to establish a standardised national pathway.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThrough analysis of how chronic pCMO is currently managed across multiple ophthalmic centres, we have identified key areas for improvement in the management of chronic pCMO.\u003c/p\u003e \u003cp\u003eChronic pseudophakic cystoid macular oedema is predominantly an inflammatory process that often fails to resolve with topical therapy alone. Our real-world data show that while half of patients respond to prolonged topical treatment, earlier escalation to corticosteroid injection \u0026ndash; either periocular triamcinolone or intravitreal dexamethasone achieves markedly faster resolution and improved anatomical outcomes.\u003c/p\u003e \u003cp\u003ePeriocular triamcinolone offers efficacy comparable to intravitreal dexamethasone, with a lower procedural risk and cost, supporting its use as a first-line escalation option in suitable patients. Anti-VEGF agents showed minimal benefit and should be reserved for eyes with coexisting vascular disease or steroid intolerance.\u003c/p\u003e \u003cp\u003eThe current delay from referral in the community to initiation of treatment in a tertiary referral centre represents suboptimal management.\u003c/p\u003e \u003cp\u003eTo optimise outcomes, pCMO management should adopt a structured, time-bound escalation pathway, with initiation of corticosteroid injection if no improvement is seen within six to eight weeks of topical therapy. Prospective trials are warranted to define optimal retreatment intervals and develop a standardised national protocol for chronic pCMO management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflicts of interest\u003c/h2\u003e \u003cp\u003eNone.\u003c/p\u003e \u003cp\u003eAll authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors did not receive support from any organisation for the submitted work.\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNone.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.K \u0026amp; B.T contributed equally as joint first authors in this work. A.K \u0026amp; B.T wrote the main manuscript text. M.K and A.H were responsible for data collection and manuscript review. M.K was responsible for study design. S.S was responsible for final manuscript review.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGrzybowski A et al (2016) Pseudophakic cystoid macular edema: update 2016. Clin Interv Aging 11:1221\u0026ndash;1229. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/CIA.S111761\u003c/span\u003e\u003cspan address=\"10.2147/CIA.S111761\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHenderson BA et al (2007) Clinical pseudophakic cystoid macular edema: risk factors and duration. J Cataract Refract Surg 33:1550\u0026ndash;1558. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jcrs.2007.05.013\u003c/span\u003e\u003cspan address=\"10.1016/j.jcrs.2007.05.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErikitola OO et al (2021) Persistent CME after uncomplicated cataract surgery: Scottish study. Eye (Lond) 35:584\u0026ndash;591. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41433-020-0908-y\u003c/span\u003e\u003cspan address=\"10.1038/s41433-020-0908-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlach AJ (1998) Cystoid macular edema after cataract surgery: incidence and treatment. Trans Am Ophthalmol Soc 96:557\u0026ndash;634\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenitah NR, Arroyo JG (2010) Pseudophakic cystoid macular edema. Int Ophthalmol Clin 50:139\u0026ndash;153\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchaub F et al (2018) Preexisting epiretinal membrane and pseudophakic CME. Graefes Arch Clin Exp Ophthalmol 256:909\u0026ndash;917. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00417-018-3954-4\u003c/span\u003e\u003cspan address=\"10.1007/s00417-018-3954-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChu CJ et al (2016) Risk factors and incidence of macular edema after cataract surgery. Ophthalmology 123:316\u0026ndash;323. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2015.10.001\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2015.10.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSivaprasad S et al (2005) NSAIDs for CME after cataract surgery: systematic review. Br J Ophthalmol 89:1420\u0026ndash;1422. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/bjo.2005.073817\u003c/span\u003e\u003cspan address=\"10.1136/bjo.2005.073817\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKessel L et al (2014) Prevention of macular edema by steroid and NSAID drops. Ophthalmology 121:1915\u0026ndash;1924. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2014.04.035\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2014.04.035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeier JS et al (2000) Ketorolac vs prednisolone vs combination therapy for pseudophakic CME. Ophthalmology 107:2034\u0026ndash;2038\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlach AJ et al (1987) Ketorolac 0.5% for chronic aphakic and pseudophakic CME. Am J Ophthalmol 103:479\u0026ndash;486. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0002-9394(14)74268-0\u003c/span\u003e\u003cspan address=\"10.1016/s0002-9394(14)74268-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlach AJ et al (1991) Improvement in visual acuity in chronic pseudophakic CME with ketorolac. Am J Ophthalmol 112:514\u0026ndash;519\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo S et al (2015) Management of pseudophakic CME. Surv Ophthalmol 60:123\u0026ndash;137. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.survophthal.2014.08.005\u003c/span\u003e\u003cspan address=\"10.1016/j.survophthal.2014.08.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConway MD et al (2003) Intravitreal triamcinolone for refractory CME. J Cataract Refract Surg 29:27\u0026ndash;33. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0886-3350(02)01441-4\u003c/span\u003e\u003cspan address=\"10.1016/s0886-3350(02)01441-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMylonas G et al (2017) Dexamethasone implant vs triamcinolone for postoperative CME. Curr Eye Res 42:648\u0026ndash;652. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/02713683.2016.1214968\u003c/span\u003e\u003cspan address=\"10.1080/02713683.2016.1214968\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBellocq D et al (2015) Dexamethasone implants for post-surgical macular edema: EPISODIC study. Br J Ophthalmol 99:979\u0026ndash;983. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/bjophthalmol-2014-306159\u003c/span\u003e\u003cspan address=\"10.1136/bjophthalmol-2014-306159\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenhamou N et al (2003) Intravitreal triamcinolone for refractory pseudophakic CME. Am J Ophthalmol 135:246\u0026ndash;249. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0002-9394(02)01938-4\u003c/span\u003e\u003cspan address=\"10.1016/s0002-9394(02)01938-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKonstantopoulos A et al (2007) Intravitreal triamcinolone for refractory CME: review. Eur J Ophthalmol 17:812\u0026ndash;821\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi YJ et al (2006) Intravitreal versus posterior subtenon injection of triamcinolone acetonide for diabetic macular edema. Korean J Ophthalmol 20:205\u0026ndash;209. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3341/kjo.2006.20.4.205\u003c/span\u003e\u003cspan address=\"10.3341/kjo.2006.20.4.205\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpitzer MS et al (2008) Bevacizumab for postoperative pseudophakic CME. J Cataract Refract Surg 34:70\u0026ndash;75. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jcrs.2007.08.021\u003c/span\u003e\u003cspan address=\"10.1016/j.jcrs.2007.08.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTasnadi B et al (2025) Lessons from a vitreoretinal virtual service in a tertiary center. Telemed J E Health 31:1236\u0026ndash;1240. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1089/tmj.2025.0042\u003c/span\u003e\u003cspan address=\"10.1089/tmj.2025.0042\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArevalo JF et al (2009) Bevacizumab for refractory pseudophakic CME: PACORES results. Ophthalmology 116:1481\u0026ndash;1487. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2009.04.006\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2009.04.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYilmaz T et al (2011) Systematic review: bevacizumab for pseudophakic CME. Clin Ophthalmol 5:923\u0026ndash;929\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKersey JP, Broadway DC (2006) Corticosteroid-induced glaucoma: review. Eye (Lond) 20:407\u0026ndash;416. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/sj.eye.6701895\u003c/span\u003e\u003cspan address=\"10.1038/sj.eye.6701895\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalcl\u0026egrave;s A et al (2017) Safety of intravitreal dexamethasone implant (OZURDEX): SAFODEX study. Retina 37:1352\u0026ndash;1359. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/IAE.0000000000001369\u003c/span\u003e\u003cspan address=\"10.1097/IAE.0000000000001369\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhurana RN et al (2014) Dexamethasone implant migration: risk factors and management. Ophthalmology 121:67\u0026ndash;71. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ophtha.2013.06.033\u003c/span\u003e\u003cspan address=\"10.1016/j.ophtha.2013.06.033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\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":"","lastPublishedDoi":"10.21203/rs.3.rs-8429068/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8429068/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePseudophakic cystoid macular oedema (pCMO) is a common complication following cataract surgery. Chronic pCMO is defined as oedema persisting for 90 days or longer postoperatively. No consensus currently exists regarding optimal management, resulting in considerable variability in clinical practice. This study aimed to evaluate current treatment approaches for chronic pCMO across Greater Glasgow area.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective cohort study was conducted on cases referred by community optometrists between January 2021 and December 2023 for post cataract surgery cystoid macular oedema (CMO). Inclusion criteria were OCT-confirmed oedema persisting for at least 90 days postoperatively. Exclusion criteria included postoperative CMO attributable to other causes, resolution within 90 days, or prior fovea involving diabetic macular oedema. Electronic health records and OCT images were reviewed to confirm diagnosis, collect demographic data, treatment regimens, duration, recurrence, and adverse effects of treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThirty-four eyes from thirty-four patients were included in the study. The median time to resolution of chronic pCMO from diagnosis was 164 days. Median resolution times by treatment were as follows: exclusive topical therapy (ETT) 130 days; topicals plus intravitreal dexamethasone implant (TT-IDI) 177.5 days; topicals plus periocular triamcinolone acetonide (TT-PTA) 275 days; topicals plus intravitreal triamcinolone acetonide (TT-ITA) 123 days; and topicals plus intravitreal anti-VEGF (TT-AntiVEGF) 264 days. After escalation to adjuvant therapy, median resolution times were IDI 56.5 days; PTA 29 days; ITA 73 days; Anti-VEGF 124 days. Median time to escalation to adjuvant therapy was 108 days. Two patients experienced CMO recurrence at three and six months, respectively and one (2.9%) developed a steroid response.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eManagement of chronic pCMO varied substantially, with a median 108-day delay before escalation to invasive therapies, reflecting caution to escalate. Among adjuvant therapies, periocular triamcinolone and intravitreal dexamethasone demonstrated the most favourable resolution times, highlighting inflammation as the principal driver of chronic pCMO. In contrast, anti-VEGF therapy showed limited benefit. A median 40-day delay between referral and treatment initiation suggests potential for improved efficiency, particularly if initial topical therapy is commenced earlier by the referring optometrist. Earlier escalation to periocular or intravitreal corticosteroid therapy after 6-8 weeks of inadequate topical response may enhance outcomes.\u003c/p\u003e","manuscriptTitle":"Comparative real-world outcomes of treatment protocols for chronic pseudophakic cystoid macular oedema","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 06:18:11","doi":"10.21203/rs.3.rs-8429068/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":"107d0df1-9998-48dc-91a7-c453e7bf4959","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T06:18:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 06:18:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8429068","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8429068","identity":"rs-8429068","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}