Optical coherence tomography angiography measurements in systemic lupus erythematosus: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting various organs. Ocular involvement, particularly retinopathy, is common, emphasizing the significance of early detection. Optical coherence tomography angiography (OCTA), a non-invasive imaging technique, reveals microvascular changes, aiding SLE diagnosis and monitoring. This study evaluates OCTA's effectiveness in detecting SLE-related retinal alterations. A systemic search was undertaken across PubMed, Embase, and Scopus databases to identify studies presenting OCTA measurements in SLE patients compared to healthy controls. The meta-analysis, employing either fixed-effects or random-effects models based on heterogeneity levels, was conducted. Additionally, subgroup and sensitivity analyses, meta-regression, and quality assessments were carried out. Thirteen studies of 565 eyes in the SLE group, and 560 eyes in the control group were included. The meta-analyses revealed that SLE patients had a significantly lower retinal vessel density in the superficial and deep capillary plexus layers, choriocapillaris flow area, and foveal avascular zone (FAZ) circularity index compared to healthy controls, but that there were no significant differences in the FAZ area and perimeter. These findings highlight how OCTA can provide a noninvasive assessment of SLE effects on the retinal microvasculature, potentially presenting a reliable biomarker for more precise detection of SLE and disease activity monitoring.

Association of the Complement Factor H Y402H Polymorphism and Response to Anti-Vascular Endothelial Growth Factor Treatment in Age-related Macular Degeneration: An Updated Meta-analysis.

INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) agents have a variable effect on patients with age-related macular degeneration (AMD) that has been attributed to several causes, including genetic factors. We evaluated the effects of Complement Factor H (CFH) rs1061170/Y402H polymorphism on the response to anti-VEGF therapy among AMD patients. METHODS: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were used for a literature search. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated to assess the effects of CFH Y402H polymorphism on the response to anti-VEGF therapy in AMD. I2 was used to present the amount of heterogeneity. We used STATA version 14.0 software. RESULTS: Twenty-five papers reporting data for 4681 patients were included in this study. Better response to anti-VEGF therapy was seen in T over C (OR=1.25, 95%CI=1.04-1.50), TT over CC (OR=1.60, 95%CI=1.06-2.4), and TT+TC over CC (OR=1.68, 95%CI=1.23-2.28) genotypes. There was no significant difference in three other genetic models (TT vs. TC, TT vs. TC+CC, TC vs. TT+CC). In Asians, no significant difference was observed in all six genetic models. Ranibizumab and bevacizumab had similar efficacy; however, conbercept was more effective in homozygous genotypes. The literature indicated that TT and TC genotypes and T allele were associated with a better functional response, while the CC genotype and C alleles had a better anatomical response. The combination of risk alleles in ARMS2 A69S (rs10490924), VEGF-A (rs699947), and VEGF-A (rs833069) with Y420H is a predictor of non-respondents. CONCLUSION: In patients with AMD, the CFH Y402H is a predictor of the response to anti-VEGF agents and should be considered in the treatment plan.

Optical coherence tomography angiography in diabetic retinopathy: A major review.

Diabetic retinopathy (DR) is characterized by retinal vasculopathy and is a leading cause of visual impairment. Optical coherence tomography angiography (OCTA) is an innovative imaging technology that can detect various pathologies and quantifiable changes in retinal microvasculature. We briefly describe its functional principles and advantages over fluorescein angiography and perform a comprehensive review on its clinical applications in the screening or management of people with prediabetes, diabetes without clinical retinopathy (NDR), nonproliferative DR (NPDR), proliferative DR (PDR), and diabetic macular edema (DME). OCTA reveals early microvascular alterations in prediabetic and NDR eyes, which may coexist with sub-clinical neuroretinal dysfunction. Its applications in NPDR include measuring ischemia, detecting retinal neovascularization, and timing of early treatment through predicting the risk of retinopathy worsening or development of DME. In PDR, OCTA helps characterize the flow within neovascular complexes and evaluate their progression or regression in response to treatment. In eyes with DME, OCTA perfusion parameters may be of predictive value regarding the visual and anatomical gains associated with treatment. We further discussed the limitations of OCTA and the benefits of its incorporation into an updated DR severity scale.

Safe Viewing of Solar Eclipses.

This JAMA Patient Page describes solar eclipses and how to view them safely.

Choroidal thickness in eyes of rheumatoid arthritis patients measured using optical coherence tomography: A systematic review and meta-analysis.

Rheumatoid arthritis (RA), an autoimmune disease, affects eyes in 25% of cases. Retinal alterations in RA can function as biomarkers as early risk indicators for developing sight-threatening conditions. Optical coherence tomography (OCT) provides high-resolution images of the retina and its component's thickness measures. The purpose of this review is to compare the choroidal thickness (CT) of RA patients and healthy controls. We examined the databases of PubMed, Scopus, and Embase. Depending on the heterogeneity, an appropriate model was used for the meta-analysis. Additionally, meta-regression, publication bias, subgroup analyses, and quality evaluation were carried out. We evaluated 8 studies involving 363 RA patients and 343 healthy controls. Our findings demonstrated that RA participants had significantly lower CT at 500 and 1500 µm nasal and temporal to the fovea compared to controls. The subfoveal, 1000 µm temporal and nasal to the fovea, and average CT, however, did not demonstrate statistical significance. The results of this study demonstrate that choroidal thickness is different in RA patients from healthy controls in several areas. OCT measurements may be related to both the visual acuity and the possibility of developing several rheumatic-ophthalmic problems. Future research is thus needed to get more firm findings.

Severe Intraocular Inflammation Following Intravitreal Faricimab.

Importance: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents. Objective: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution. Design, Setting, and Participants: In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023. Exposure: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab. Main Outcomes and Measures: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging. Results: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3. Conclusions and Relevance: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.

Ocular, Visual, and Anatomical Outcomes in Eyes Requiring Incisional Intraocular Pressure-Lowering Surgery Following the 0.19-mg Fluocinolone Acetonide Intravitreal Implant.

BACKGROUND AND OBJECTIVE: To assess ocular, visual, and anatomical outcomes following the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) and incisional intraocular pressure (IOP)-lowering surgery in diabetic macular edema. PATIENTS AND METHODS: From a 36-month, phase 4, open-label, observational study (N = 202 eyes, 159 patients), 8 eyes (7 patients) required IOP-lowering surgery post-FAc; eyes were segregated by FAc-induced (n = 5, 2.47%) versus neovascular glaucoma (NVG)-related (n = 3, 1.49%) IOP elevations and assessed for IOP, best corrected visual acuity (BCVA), central subfield thickness (CST), and cup-to-disc ratio (c/d). RESULTS: Changes at 36 months were +5.4 letters BCVA (P > 0.05) and +0.09 c/d (P = 0.0217); IOP and CST were unchanged. FAc-induced-group eyes required fewer IOP-lowering medications than NVG-group eyes (2.0 versus 4.0; P < 0.01) but for longer duration (15.2 versus 2.6 months; P < 0.001). CONCLUSIONS: Post-FAc IOP-lowering surgery, regardless of cause, largely did not affect the outcomes measured; these procedures, then, may not meaningfully threaten positive outcomes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:22-29.].

Treating patients with geographic atrophy: are we there yet?

Geographic atrophy (GA) is a progressive degenerative disease that significantly contributes to visual impairment in individuals aged 50 years and older. The development of GA is influenced by various modifiable and non-modifiable risk factors, including age, smoking, and specific genetic variants, particularly those related to the complement system regulators. Given the multifactorial and complex nature of GA, several treatment approaches have been explored, such as complement inhibition, gene therapy, and cell therapy. The recent approval by the Food and Drug Administration of pegcetacoplan, a complement C3 inhibitor, marks a significant breakthrough as the first approved treatment for GA. Furthermore, numerous interventions are currently in phase II or III trials, alongside this groundbreaking development. In light of these advancements, this review provides a comprehensive overview of GA, encompassing risk factors, prevalence, genetic associations, and imaging characteristics. Additionally, it delves into the current landscape of GA treatment, emphasizing the latest progress and future considerations. The goal of starting this discussion is to ultimately identify the most suitable candidates for each therapy, highlight the importance of tailoring treatments to individual cases, and continue monitoring the long-term implications of these emerging interventions.

Age-related macular degeneration and neurodegenerative disorders: Shared pathways in complex interactions.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly, and neurodegenerative disorders such as Alzheimer disease and Parkinson disease are debilitating conditions that affect millions worldwide. Despite the different clinical manifestations of these diseases, growing evidence suggests that they share common pathways in their pathogenesis including inflammation, oxidative stress, and impaired autophagy. In this review, we explore the complex interactions between AMD and neurodegenerative disorders, focusing on their shared mechanisms and potential therapeutic targets. We also discuss the current opportunities and challenges for developing effective treatments that can target these pathways to prevent or slow down disease progression in AMD. Some of the promising strategies that we explore include modulating the immune response, reducing oxidative stress, enhancing autophagy and lysosomal function, and targeting specific protein aggregates or pathways. Ultimately, a better understanding of the shared pathways between AMD and neurodegenerative disorders may pave the way for novel and more efficacious treatments.

An update on visual prosthesis.

PURPOSE: To review the available evidence on the different retinal and visual prostheses for patients with retinitis pigmentosa and new implants for other indications including dry age-related macular degeneration. METHODS: The PubMed, GoogleScholar, ScienceDirect, and ClinicalTrials databases were the main resources used to conduct the medical literature search. An extensive search was performed to identify relevant articles concerning the worldwide advances in retinal prosthesis, clinical trials, status of devices and potential future directions up to December 2022. RESULTS: Thirteen devices were found to be current and were ordered by stimulation location. Six have active clinical trials. Four have been discontinued, including the Alpha IMS, Alpha AMS, IRIS II, and ARGUS II which had FDA and CE mark approval. Future directions will be presented in the review. CONCLUSION: This review provides an update of retinal prosthetic devices, both current and discontinued. While some devices have achieved visual perception in animals and/or humans, the main issues impeding the commercialization of these devices include: increased length of time to observe outcomes, difficulties in finding validated meaures for use in studies, unknown long-term effects, lack of funding, and a low amount of patients simultaneously diagnosed with RP lacking other comorbid conditions. The ARGUS II did get FDA and CE mark approval so it was deemed safe and also effective. However, the company became more focused on a visual cortical implant. Future efforts are headed towards more biocompatible, safe, and efficacious devices.

Early-Phase Perceptions of COVID-19's Impact on Ophthalmology Practice Patterns: A Survey from the Pan-American Association of Ophthalmology.

Purpose: The COVID-19 pandemic affected medical practice worldwide due to interventions to prevent spreading. Its effect on ophthalmology practices in Latin America has not yet been explored. We aimed to assess the perceptions about the pandemic from countries' ophthalmological national and subspecialty retina societies affiliated to the Pan-American Association of Ophthalmology (PAAO). Patients and Methods: A survey-based study of leaders of national ophthalmological and retinal societies was conducted. The survey was sent by email to 30 societies, from which 20 responded (12 countries, 66.6% response rate). It included closed- and open-ended questions about (1) operational capacity and precautions, (2) telemedicine and virtual care, (3) procedures, and (4) post-pandemic considerations. Results: There was a marked decline in ophthalmology patient visits (80-95%) and elective surgeries (90%) during 2020 compared to before the pandemic. Precautions like temperature checks, mask usage, and social distancing were widely implemented while personal protective equipment (PPE) availability varied. Telemedicine use was limited due to lack of experience with it. Reopening plans focused on maintaining precautions and gradually resuming activities. Economic and security concerns were raised, and adherence to guidelines was emphasized. Respondents acknowledged the need to adapt to a "new normal". Long duration drugs, fewer imaging studies, and shorter wait times were preferred; however, availability of long duration drugs was limited. Conclusion: The pandemic impacted ophthalmology in Latin America, with reduced patient visits, procedures, and surgeries. Delayed treatment and complications were likely the result of the pandemic.

Early Vitrectomy for Endophthalmitis: Are EVS Guidelines Still Valid?

BACKGROUND: Endophthalmitis, a potentially sight-threatening condition, remains a challenge for ophthalmologists worldwide. The endophthalmitis vitrectomy study (EVS) conducted in 1995 compared vitrectomy and intravitreal antibiotic injections to intravitreal antibiotic injections alone for acute post-cataract surgery and secondary intraocular lens endophthalmitis, setting treatment guidelines. However, the landscape of clinical practice has evolved considerably since then, raising questions about the applicability of EVS recommendations today. SUMMARY: Recent studies have proposed that early and complete vitrectomy (CEVE) could potentially be an effective approach for managing endophthalmitis cases, irrespective of the initial visual acuity. However, it is important to note that the level of rigor in these recent studies may not match that of the EVS study, and as such, this assertion should be considered with caution. Furthermore, the EVS study exclusively focused on post-cataract surgery cases, leaving other endophthalmitis types, like post-intravitreal injection and post-traumatic endophthalmitis, without standardized treatment guidelines. Research exploring the role of early vitrectomy in these contexts yields mixed results, emphasizing the need for further investigation and well-designed prospective trials. Endogenous endophthalmitis, originating from systemic infections, adds complexity to the scenario. While early vitrectomy shows promise in specific cases, conflicting evidence necessitates comprehensive research. KEY MESSAGES: This review underscores the necessity for tailored treatment strategies, supporting early vitrectomy when clinically indicated, and advocating for prospective trials to clarify its role in diverse endophthalmitis scenarios. As surgical techniques and antimicrobial therapies continue to advance, reevaluating treatment paradigms becomes crucial to enhance patient outcomes and protect ocular health.

Current Management of Subretinal Hemorrhage in Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among individuals aged 65 years and older in the USA. For individuals diagnosed with AMD, approximately 12% experience varying levels of subretinal hemorrhage (SRH), which can be further classified by size into small, medium, and massive measured in disc diameters. SRH is an acute and rare sight-threatening complication characterized by an accumulation of blood under the retina arising from the choroidal or retinal circulation. Released iron toxins, reduced nutrient supply, fibrin meshwork contraction, and outer retinal shear forces created by SRH contribute to visual loss, macular scarring, and photoreceptor damage. SRH treatment strategies aim to displace hemorrhage from the foveal region and prevent further bleeding. Although there are no standardized treatment protocols for SRH, several surgical and nonsurgical therapeutical approaches may be employed. The most common surgical approaches that have been utilized are pars plana vitrectomy (PPV) combined with multiple maneuvers such as the removal of choroidal neovascularization lesions, macular translocation, retinal pigment epithelium patch repair, SRH drainage, intravitreal injection of recombinant-tissue plasminogen activator (tPA), expansile gas and air displacement, and anti-vascular endothelial growth factor (anti-VEGF) injections. Nonsurgical therapeutical approaches include intravitreal anti-VEGF monotherapy, intravitreal tPA administration without PPV, and photodynamic therapy. This review article aims to explore the current treatment strategies and supporting literature regarding both surgical and nonsurgical, of SRH in patients with AMD. Moreover, this article also aims to highlight the distinct treatment modalities corresponding to different sizes of SRH.

Artificial intelligence in retinal image analysis: Development, advances, and challenges.

Modern advances in diagnostic technologies offer the potential for unprecedented insight into ophthalmic conditions relating to the retina. We discuss the current landscape of artificial intelligence in retina with respect to screening, diagnosis, and monitoring of retinal pathologies such as diabetic retinopathy, diabetic macular edema, central serous chorioretinopathy, and age-related macular degeneration. We review the methods used in these models and evaluate their performance in both research and clinical contexts and discuss potential future directions for investigation, use of multiple imaging modalities in artificial intelligence algorithms, and challenges in the application of artificial intelligence in retinal pathologies.

Surgical Management of Diabetic Macular Edema.

PURPOSE OF REVIEW: Diabetic macular edema (DME) is the accumulation of fluid in the extracellular space within the macula and is a major cause of visual impairment among patients with diabetes. First-line treatment for DME includes pharmacotherapy with intravitreal anti-vascular endothelial growth factor medications and intravitreal corticosteroids. Alternative therapeutic strategies include laser photocoagulation for non-center involving DME, and surgical options such as pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peel in cases with vitreoretinal interface anomalies or DME refractory to pharmacotherapy, and the Port Delivery System (PDS) for sustained release of anti-vascular endothelial growth factor (VEGF) medication. Our aim is to review the existing literature on surgical management of DME including imaging changes in chronic DME and the clinical relevance of surgical intervention. RECENT FINDINGS: Imaging changes associated with DME and a worse prognosis include disorganization of the retinal layer, disruption of both the external limiting membrane (ELM) and ellipsoid zone, and vitreomacular interface abnormalities. Studies involving pars plana vitrectomy with and without ILM peel show anatomic improvement but may not always be associated with significant change in visual outcomes. Early studies lacked detailed imaging of the retinal layers and PPV was likely performed as a last resort. In addition, the novel PDS is surgically implanted into the pars plana and works as a drug reservoir with controlled release of drug. However, it has been recalled in patients with wet age-related macular degeneration due to issues with dislodgement. Surgical interventions for DME include pars plana vitrectomy with and without ILM peel and new surgical therapies for DME such as the PDS and subretinal gene therapy have the potential to reduce the risk of DME progression.

Pre-operative intravitreal bevacizumab for tractional retinal detachment secondary to proliferative diabetic retinopathy: the Alvaro Rodriguez lecture 2023.

The treatment of proliferative diabetic retinopathy (PDR) has evolved significantly since the initial use of panretinal photocoagulation as a treatment in the 1950s. Vascular endothelial growth factor inhibitors have provided an effective alternative without the risk of peripheral vision loss. Despite this, the risk of complications requiring surgical intervention in PDR remains high. Intravitreal bevacizumab has shown promise as a preoperative adjuvant to vitrectomy for PDR complications, albeit with a purported risk for tractional retinal detachment (TRD) progression in eyes with significant fibrous proliferation. Here we will discuss anti-VEGF agent use in PDR and its role in surgical intervention for PDR complications including TRD.

Optical coherence tomography angiography measurements in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Recent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography-angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue. METHODS: PubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level. RESULTS: The study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (both P < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (all P < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (all P < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (both P < 0.0001). CONCLUSIONS: This systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities.

Endophthalmitis Following Inadvertent Intraocular Botulinum Toxin A Injection.

Botulinum toxin A injection is a safe alternative procedure to surgery in the management of different types of strabismus. Serious complications such as globe perforation are rare in expert hands. The authors report a case of a child known to have a muscle-eye-brain disease with high myopia who developed endophthalmitis following inadvertent penetrating intraocular botulinum toxin A injection for strabismus correction. To their knowledge, this serious complication after penetrating botulinum toxin A injection has not been previously reported. [J Pediatr Ophthalmol Strabismus. 2023;60(2):e8-e10.].

International Validation of Myopic Traction Maculopathy Staging System.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the interobserver agreement of the myopic traction maculopathy (MTM) staging system (MSS). PATIENTS AND METHODS: Each observer was asked to look at the MSS Table and then identify, in each optical coherence tomography scan, one among four stages of MTM in the retina, one among three stages in the fovea, and, as secondary findings, the presence or absence of an outer lamellar macular hole and the presence or absence of epiretinal abnormalities. The interobserver agreement value was calculated using the Gwet's AC1 unweighted and AC2 weighted statistics. The outcomes were interpreted as poor (<0.00), slight (0.00 to 0.20), fair (0.21 to 0.40), moderate (0.41 to 0.60), substantial (0.61 to 0.80), or almost perfect (0.81 to 1.00) agreement. RESULTS: The agreement, among 65 participants, was 0.62 (AC1) and 0.77 (AC2) for the retina stage; 0.63 (AC1) and 0.81 (AC2) for the fovea stage; 0.56 (AC1) for the outer lamellar macular hole; and 0.26 (AC1) for epiretinal abnormalities. CONCLUSION: The MSS is highly reproducible and helps ophthalmologists to share information on MTM in a more accurate and reliable way. [Ophthalmic Surg Lasers Imaging Retina 2023;54(3):153-157.].

DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR.

PURPOSE: To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting. METHODS: Retrospective review of secondary MH surgeries. RESULTS: A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into this study with a mean MH size of 762 µ m and a mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.11 (∼20/260 Snellen). Closure rates were 89.3% for tissue transplantation, 77.3% for internal limiting membrane (ILM) flaps, 92.9% for MH manipulation, and 12.5% for repeat ILM peeling ( P < 0.05). Best-corrected visual acuity changes in logarithm of the minimum angle of resolution from baseline to postoperative month six were +0.29 for ILM peeling alone (15 Early Treatment Diabetic Retinopathy Study letters worse), -0.39 for MH manipulation (20 Early Treatment Diabetic Retinopathy Study letters improved), -0.23 for tissue transplantation (13 Early Treatment Diabetic Retinopathy Study letters improved), and -0.2 for ILM flaps (10 Early Treatment Diabetic Retinopathy Study letters improved; P < 0.05). CONCLUSION: Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of approximately 750 eyes.