Assessing the subjective quality of smartphone anterior segment photography: a non-inferiority study.

PURPOSE: To assess the subjective quality of anterior segment photos taken from a smartphone camera adapted to the slit lamp compared to a commercial inbuilt slit-lamp camera. METHODS: Non-inferiority study. Five paired images of the anterior segment of normal eyes were taken using an iPhone 11 (Apple, Inc., Calif., USA) camera attached to a universal slit-lamp adaptor and a commercial inbuilt slit-lamp camera (Haag-Streit Diagnostics, Bern, Switzerland). Images were collated into a survey in which ophthalmology students, residents, registrars, and consultants participated to select the image taken from the inbuilt slit-lamp camera. If the image quality was subjectively indistinguishable, we expected a 50:50 split for each photograph that was presented. We selected a 10% non-inferiority margin, with the hypothesis that no less than 40% of images believed to be from the conventional camera were in fact from the smartphone camera. RESULTS: There were 27 respondents in the survey: ophthalmology consultants (n = 7), registrars (n = 10), residents (n = 7), intern (n = 1) and students (n = 2). The mean correct identification across the respondents was 11.3 out of 25 (45.2%) images. Overall, the smartphone camera was non-inferior to the inbuilt slit-lamp camera (p < 0.001). The non-inferiority of the smartphone camera was significant for consultants (47.4%, p < 0.01), registrars (47.6%, p < 0.001) and residents (37.7%, p < 0.0001). CONCLUSIONS: Anterior segment images obtained with a smartphone camera were non-inferior to the commercial inbuilt slit-lamp camera. Smartphone cameras may be a non-inferior tool for communication of anterior segment images having implications for the ease of access to quality telehealth consultations.

Rates of diabetic retinopathy screening in pregnant patients with type 1 and type 2 diabetes in a predominantly Indigenous Central Australian population.

BACKGROUND: Pregnancy is a risk factor for the progression of diabetic retinopathy (DR) in women with pre-gestational diabetes. Australian screening guidelines recommend DR screening in the first trimester of pregnancy. The rates of DR screening in pregnant patients with pre-gestational diabetes are unknown in Australia. AIM: To determine the rates of DR screening in pregnant women with pre-gestational diabetes at Alice Springs Hospital Diabetes Antenatal Care and Education (DANCE) clinic. MATERIALS AND METHODS: Retrospective review of women with pre-gestational diabetes who attended the DANCE clinic between July 2016 and June 2020. RESULTS: There were 146 pregnancies in 144 individual women included in this review. There were 93% (n = 134) who identified as Aboriginal but not Torres Strait Islander. DR screening was performed in 23 (16%) pregnancies, in which DR was present in six (26%) and no retinal abnormality was found in 17 (74%). Of seven (5%) women who had a history of DR, only three had a screen during the pregnancy period. The location of the DR screen included Alice Springs Hospital (17%, n = 4), Alice Springs general practice clinics (35%, n = 8) and remote NT community clinics outside of Alice Springs (39%, n = 9). The trimesters in which women received their DR screens were: trimester 1, 45%, n = 10; trimester 2, 39%, n = 9; trimester 3, 17%, n = 4. CONCLUSION: The minority of pregnant women who attend the DANCE clinic at Alice Springs Hospital received DR screening in adherence with national guidelines.

Efficacy of intracameral antibiotics following manual small incision cataract surgery in reducing the rates of endophthalmitis: A meta-analysis.

BACKGROUND: Manual small incision cataract surgery (MSICS) is a widely used technique for cataract surgery in the developing world. Higher rates of postoperative endophthalmitis have been reported with this technique compared with phaco-emulsification. The purpose of this study was to evaluate the efficacy of prophylactic intracameral (IC) antibiotics in reducing the rates of postoperative endophthalmitis following MSICS. METHODS: Systematic review and meta-analysis of patients undergoing MSICS. A literature search in PubMed and EMBASE databases was performed to identify studies published from October 1992 to April 2020 evaluating MSICS with a minimum of 500 eyes reported. Two authors independently assessed eligibility, extracted data and assessed the risk of bias. Heterogeneity was assessed using the I2 test. RESULTS: Twelve studies enrolling 1 494 307 eyes were included. IC antibiotics were used in 725 324 (48.5%) eyes. The risk ratio of developing endophthalmitis was 2.94 (95% CI, 1.07-8.12; P = .037) in eyes that did not receive IC antibiotics. CONCLUSIONS: Routine use of IC antibiotics may help to reduce the rates of endophthalmitis following MSICS and significantly improve the safety of this effective form of cataract surgery.

Primary Nasocutaneous Fistulae in Granulomatosis With Polyangiitis: A Case Series and Literature Review.

PURPOSE: To report the presentation, investigation, management, and outcomes of primary nasocutaneous fistulae in granulomatosis with polyangiitis and review the literature of this complication. METHODS: Retrospective series of 5 patients with granulomatosis with polyangiitis and nasocutaneous fistulae and the medical and surgical management strategies employed. RESULTS: Two cases presented with fistulae as the primary symptom of their systemic disease. Systemic management of granulomatosis with polyangiitis is a primary concern and two cases had inadequate control at presentation such that surgical intervention was deferred. Of the other 3 cases, 2 were closed using a median forehead flap and the other with an orbicularis advancement flap. An endonasal approach was attempted in 1 case but was unsuccessful due to the friable nature of the nasal mucosal tissue. CONCLUSIONS: Nasocutaneous fistulae should alert the clinician to underlying granulomatosis with polyangiitis, which may be a presentation of this condition. Systemic management of disease is often a barrier to surgical management. Myocutaneous flaps may be the most reliable management option to achieve closure.

AFLIBERCEPT FOR PERSISTENT DIABETIC MACULAR EDEMA: Forty-Eight-Week Outcomes.

PURPOSE: To evaluate functional and anatomical outcomes after a switch from intravitreal bevacizumab to aflibercept in patients with persistent diabetic macular edema. METHODS: Prospective, single-arm, open-label clinical trial of patients with persistent diabetic macular edema, despite previous treatment with bevacizumab. Five loading doses of intravitreal aflibercept were administered every 4 weeks with subsequent injections administered every 8 weeks. Patients were reviewed every 4 weeks, and best-corrected visual acuity and central macular thickness were recorded. Primary outcome measures included change in central macular thickness and best-corrected visual acuity at week 48 compared with baseline. Paired t-tests were used to assess change between baseline and follow-up visits. RESULTS: At baseline, 43 eyes from 43 patients were recruited with a median (interquartile range) of 12 (7-24) previous intravitreal anti-vascular endothelial growth factor injections over a period of 18 (8-34) months. Mean ± SD central macular thickness reduced by 59 ± 114 µm (P = 0.002), and best-corrected visual acuity improved by 3.9 ± 7.0 letters (P = 0.001) after 48 weeks in the 41 patients who completed the trial. Best-corrected visual acuity improvements were more marked in patients who gained ≥5 letters after the first injection (8.9 ± 5.7 vs. 1.8 ± 6.5 letter gain at 48 weeks, P = 0.002), a difference which remained significant after regression analysis with baseline best-corrected visual acuity . Vision gains and central macular thickness reduction were similar in 9 fellow eyes eligible for inclusion being concurrently treated for diabetic macular edema with bevacizumab. CONCLUSION: Intravitreal aflibercept was effective in improving anatomical and visual outcomes among patients with an incomplete response to intravitreal bevacizumab with 48 weeks of follow-up. Patients with a good early response subsequent to switching had a better improvement in vision at 48 weeks.

Effects of VEGF inhibitors on human retinal pigment epithelium under high glucose and hypoxia.

BACKGROUND: Retinal pigment epithelium (RPE) is known to secrete factors important for retinal homeostasis. How this secretome changes in diabetic eyes treated with anti-vascular endothelial growth factor (VEGF) inhibitors is unclear. METHODS: Diabetic conditions were simulated in vitro using ARPE-19 cell-line culture, with high glucose (25 mM) culture media, and hypoxia was chemically induced using cobalt chloride. Stress was assessed using cell viability assays as well as Western blots and enzyme-linked immunosorbent assay (ELISA) for production of HIF-1a and VEGF-A. Production of neurotrophic factors was quantified once conditions were established using ELISA under stress with and without the addition of VEGF inhibitors. Changes were analysed with one-way ANOVA. RESULTS: Hypoxia downregulated pigment epithelium-derived factor (PEDF) expression. The addition of bevacizumab, ranibizumab and aflibercept in normoxic conditions all led to a significant downregulation of PEDF. Glucose concentration had no effect on secretion of PEDF. Brain-derived neurotrophic factor (BDNF) secretion was downregulated in high glucose and was upregulated in hypoxia. Placental growth factor (PlGF) secretion by ARPE-19 was undetectable by ELISA. CONCLUSIONS: We found that hypoxia, high glucose or VEGF inhibitors affected secretion of neurotrophic factors. This variation under different conditions may influence neuron and photoreceptor survival in the diabetic state and VEGF inhibitor treated eyes.

Characterization of canonical Wnt signalling changes after induced disruption of Müller cell in murine retina.

Müller cells are the primary glia in the retina, playing a critical role in retinal homeostasis and retinal pathology. This study evaluated the canonical Wnt signalling pathway and its downstream effects on retinal degeneration in a transgenic mouse model of inducible Müller cell disruption. Increased expression of the LacZ reporter gene in the retina suggested Wnt signalling had been activated after induced Müller cell disruption. Activation was validated by observing nuclear translocation of ß-Catenin. The mRNA expression of 80 Wnt related genes were assessed using real-time PCR. The Wnt signalling inhibitors Dkk1, Dkk3 and sFRP3 were significantly downregulated. Furthermore, the ubiquitin-mediated ß-Catenin proteolysis genes ß-TrCP and SHFM3, were also significantly downregulated. The downstream target genes of the Wnt signalling, including Fra1, CyclinD2 and C-Myc were upregulated. The changes of these genes at the protein level were validated by Western blot. Their distributions in the retina were evaluated by immunofluorescent staining. Our findings indicate that Müller cells are involved in retinal Wnt signalling. Activation of Wnt signalling and its downstream target genes may play important roles in photoreceptor degeneration and neovascularization occurring in the retina after induced disruption of Müller cells.

Switching therapy from bevacizumab to aflibercept for the management of persistent diabetic macular edema.

PURPOSE: To evaluate the visual and anatomical outcomes following switching therapy from bevacizumab to aflibercept in patients with persistent diabetic macular edema (DME). METHODS: Patients with DME and central macular thickness (CMT) >300 µm on spectral domain optical coherence tomography (SD-OCT) despite at least 4 intravitreal bevacizumab injections in the prior 6 months were recruited for this prospective, single-armed, single centre, open-label clinical trial. Five loading doses of intravitreal aflibercept were administered every 4 weeks until week 16, at which point the treatment interval was extended to 8 weeks. All participants were reviewed every 4 weeks. At each visit, examination included best-corrected visual acuity (BCVA) measured with an Early Treatment of Diabetic Retinopathy Study chart and CMT measured with SD-OCT. Primary outcome measures were change in CMT and BCVA at week 24 compared with baseline. RESULTS: A total of 43 eyes from 43 patients were recruited for the study. At enrolment, study eyes had a mean ± standard deviation of 16.6 ± 11.5 previous intravitreal anti-VEGF injections over a period of 26.9 ± 23.8 months. Mean CMT reduced from 417 ± 91 µm at baseline to 380 ± 102 µm at 24 weeks (mean reduction 37 µm, p < 0.01). Mean BCVA improved from 67.8 ± 10.3 letters at baseline to 71.0 ± 10.1 letters at 24 weeks (mean 3.2 letter gain, p < 0.01). Eyes improving by ≥5 letters at 4 weeks following the first injection had improved vision outcomes at 24 weeks (6.8 ± 7.1 letters vs. 1.0 ± 4.7 letters, p < 0.01). CONCLUSION: Intravitreal aflibercept was effective in improving anatomical and visual outcomes among patients with incomplete response to intravitreal bevacizumab with 24 weeks of follow up. CLINICAL TRIAL REGISTRATION: ACTRN12614001307695.

Diabetic macular oedema: pathophysiology, management challenges and treatment resistance.

Diabetic macular oedema (DMO) is the leading cause of vision loss in patients living with diabetes. DMO results from hyperglycaemia-induced activation of pathways that lead to oxidative stress and release of cytokines, impairing the inner and outer blood-retinal barriers. Improved understanding of the pathophysiological mechanisms leading to DMO have led to the development of effective therapies, including vitreoretinal surgery, laser photocoagulation, intravitreal anti-vascular endothelial growth factor drugs and corticosteroids. Advances in imaging, including fluorescein angiography and optical coherence tomography, have also enhanced diagnosis and management of the condition. Despite these advances, there remain patients who do not respond completely to therapy, reflecting the complex pathophysiology of DMO. These patients may be considered treatment-resistant. In this review, we summarise the pathophysiology of DMO, as well as the available treatments and their mechanism of action. Additionally, we focus on treatment-resistant disease and review the literature on potential options for managing this complication of diabetes.

Long-term outcomes after adjunctive topical 5-flurouracil or mitomycin C for the treatment of surgically excised, localized ocular surface squamous neoplasia.

BACKGROUND: To report rates of recurrence and complications of localized ocular surface squamous neoplasia treated with 5-fluorouracil or mitomycin C as adjunctive treatment to surgical excision. DESIGN: Long-term follow up of two prospective, non-comparative interventional case series. PARTICIPANTS: One hundred fifty-three eyes with histologically confirmed localized, non-invasive ocular surface squamous neoplasia. 89 eyes were treated with adjuvant 5-fluorouracil and 64 eyes were treated with adjuvant mitomycin C. METHODS: Following surgical excision±cryotherapy patients received topical 5-fluorouracil 1% four times daily for two weeks or topical mitomycin C 0.04% four times daily for two to three 1-week cycles. MAIN OUTCOME MEASURES: Ocular surface squamous neoplasia recurrence, complications of therapy and compliance. RESULTS: Median follow up was 33.6 (range 12-84) months and 57.9 (range 12-160) months in 5-fluorouracil and mitomycin C groups, respectively. There was one recurrence in the 5-fluorouracil group and no recurrences in the mitomycin C group. Side-effects occurred in 69% of 5-fluorouracil patients and 41% of mitomycin C patients. Five patients (6%) required intervention for treatment-related side-effects in the 5-fluorouracil group versus 11 (17%) in the mitomycin C group. No vision-threatening complications were noted. CONCLUSIONS: Long-term recurrence of localised ocular surface squamous neoplasia is rare when topical 5-fluorouracil or mitomycin C are used as adjunctive treatment to surgical excision. While side-effects are common, the majority are transient and rarely limit compliance.

The role of intravitreal anti-vascular endothelial growth factor injection in peripheral exudative hemorrhagic chorioretinopathy: A systematic review.

Anti-vascular endothelial growth factor (anti-VEGF) injections have revolutionized the field of ophthalmology, and their use in a variety of retinal diseases is growing. One target disease is peripheral exudative hemorrhagic chorioretinopathy, a disease that is uncommon and poorly understood. Despite this, there are numerous studies and case reports outlining the potential role of intravitreal injection of anti-VEGF medicines to treat it. As such, an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of anti-VEGF injections in peripheral exudative hemorrhagic chorioretinopathy. Anti-VEGF was first used in 2010 to aid in the management of peripheral exudative hemorrhagic chorioretinopathy. Since then, it has been increasingly used to manage this disease. Other potential management strategies, including laser photocoagulation, cryotherapy, photodynamic therapy, and vitrectomy are explored and compared with anti-VEGF where possible. Anti-VEGF appears to be an effective therapy in managing peripheral exudative hemorrhagic chorioretinopathy, especially when there is an exudative threat to the macula.

Scoping review of nonsurgical treatment options for macular holes.

Macular holes (MH) are full-thickness retinal defects affecting central vision. While vitrectomy with inner limiting membrane (ILM) peel is the conventional MH treatment, non-surgical alternatives are gaining interest to mitigate surgical risks. This study conducted a comprehensive literature review and analysis of nonsurgical MH management. A systematic literature search was conducted on PubMed, Embase, Scopus, and the Cochrane Library from January 1, 1973, to September 13, 2023. Treatments included laser therapy, carbonic anhydrase inhibitors (CAIs), nonsteroidal antiinflammatory drugs (NSAIDs), steroids (topical, subtenons, peribulbar, intravitreal), intravitreal gas, anti-vascular endothelial growth factors and ocriplasmin injections. Data extraction covered study details, patient characteristics, MH features, treatment outcomes, and recurrence rates. The initial search yielded 3352 articles, refined to 83 articles that met inclusion criteria following screening. Overall reported anatomical closure rates were 36% with laser photocoagulation, 37% with intravitreal ocriplasmin, 55% with intravitreal gas. Closures were more frequently observed with topical NSAIDs (79%), steroids (84%) and CAIs (73%). Closures were more often observed in patients with smaller MH and in the presence of cystic macular oedema. Although non-surgical MH management approaches show potential for conservative therapy, evidence is limited to support routine use. Stage 1 and traumatic MH may benefit from a short period of observation, but the gold standard approach for full-thickness MH remains to be vitrectomy with ILM peel.

Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial.

IMPORTANCE: Obesity is a risk factor for atrial fibrillation. Whether weight reduction and cardiometabolic risk factor management can reduce the burden of atrial fibrillation is not known. OBJECTIVE: To determine the effect of weight reduction and management of cardiometabolic risk factors on atrial fibrillation burden and cardiac structure. DESIGN, SETTING, AND PATIENTS: Single-center, partially blinded, randomized controlled study conducted between June 2010 and December 2011 in Adelaide, Australia, among overweight and obese ambulatory patients (N = 150) with symptomatic atrial fibrillation. Patients underwent a median of 15 months of follow-up. INTERVENTIONS: Patients were randomized to weight management (intervention) or general lifestyle advice (control). Both groups underwent intensive management of cardiometabolic risk factors. MAIN OUTCOMES AND MEASURES: The primary outcomes were Atrial Fibrillation Severity Scale scores: symptom burden and symptom severity. Scores were measured every 3 months from baseline to 15 months. Secondary outcomes performed at baseline and 12 months were total atrial fibrillation episodes and cumulative duration measured by 7-day Holter, echocardiographic left atrial area, and interventricular septal thickness. RESULTS: Of 248 patients screened, 150 were randomized (75 per group) and underwent follow-up. The intervention group showed a significantly greater reduction, compared with the control group, in weight (14.3 and 3.6 kg, respectively; P < .001) and in atrial fibrillation symptom burden scores (11.8 and 2.6 points, P < .001), symptom severity scores (8.4 and 1.7 points, P < .001), number of episodes (2.5 and no change, P = .01), and cumulative duration (692-minute decline and 419-minute increase, P = .002). Additionally, there was a reduction in interventricular septal thickness in the intervention and control groups (1.1 and 0.6 mm, P = .02) and left atrial area (3.5 and 1.9 cm2, P = .02). CONCLUSIONS AND RELEVANCE: In this study, weight reduction with intensive risk factor management resulted in a reduction in atrial fibrillation symptom burden and severity and in beneficial cardiac remodeling. These findings support therapy directed at weight and risk factors in the management of atrial fibrillation. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000497000.

Topical carbonic anhydrase inhibitors closing bilateral secondary macular holes and a review of literature.

PURPOSE: To present a rare occurrence of bilateral macular hole secondary to vitrectomy that was successfully treated with topical carbonic anhydrase inhibitors and to review the literature for this phenomenon. METHODS: Monthly clinical examination and optical coherence tomography (OCT) was conducted before and after eight weeks of topical 2% dorzolamide administered twice a day. RESULTS: A 62-year-old male that had bilateral giant retinal tears which were repaired with vitrectomy subsequently presented with bilateral small macular holes of size 74 and 78 microns. Patient was trialled on 2% topical dorzolamide twice a day and reviewed monthly with OCT scans. Macular hole closure was identified after four weeks of topical treatment. Conclusion: Clinical improvement with conservative measures suggests a potential first line approach to the treatment of macular holes avoiding surgery and its risk profile. We also present a review of literature regarding macular holes treated with topical carbonic anhydrase inhibitors and its mechanism of action in treating macular holes.

Calciphylaxis, beware the ophthalmic mimic: A case series.

PURPOSE: We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition. OBSERVATIONS: We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis. CONCLUSION AND IMPORTANCE: These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).

Diet and risk of visual impairment: a review of dietary factors and risk of common causes of visual impairment.

Age-related macular degeneration, diabetic retinopathy, cataract, and glaucoma remain the leading causes of visual impairment in developed nations, resulting in a substantial treatment burden on sufferers and health care systems. Despite significant advances in diagnostic testing and therapeutics, population-based strategies to reduce the burden of these diseases remain limited. However, there is some evidence that these diseases may share overlapping risk factors, particularly in regard to dietary intake and antioxidant status, and it is thus possible that dietary modification may reduce both the prevalence and severity of these conditions. In particular, dietary intake of green leafy vegetables, hyperglycemia/glycemia index, and omega-3 fatty acid intake, as well as overall dietary patterns, may affect risk of one or more of these conditions. In this review, we analyse the evidence for dietary intake and the association with these conditions, and provide insights into possible modifications that may thus simultaneously reduce the risk of visual impairment from multiple causes, including improving dietary intake of green leafy vegetables and reducing dietary glycemic index, both of which have been associated with a decreased risk of multiple causes of visual impairment.

A meta-analysis of patients with treatment-resistant macular oedema secondary to retinal vein occlusions following switching to aflibercept.

To systematically review anatomical and functional outcomes of switching therapy from bevacizumab and/or ranibizumab to aflibercept in patients with persistent macular oedema secondary to retinal vein occlusions (RVO). A systematic search of aflibercept for the treatment of persistent macular oedema secondary to branch and central RVO was performed in EMBASE, PubMed and Cochrane databases prior to June 2017. The main outcome variables described were best-corrected visual acuity (BCVA) and central macular thickness (CMT). All results were analysed and pooled using random-effects models with 95% confidence intervals (CI). Eight studies met the inclusion criteria with a total of 137 eyes, incorporating both branch and central RVO. Meta-analysis demonstrated a nonsignificant change in BCVA at 6 and 12 months following switch to aflibercept (4.40 letters, 95% CI: -3.10 to 11.90, p = 0.25 and 3.10 letters, 95% CI: -1.74 to 7.94, p = 0.21, respectively). Significant improvement in mean CMT was observed after switch to aflibercept at 6 (-256.00 µm, 95% CI: -318.00 to -194.00, p < 0.001) but not 12 months (-118.00 µm, 95% CI: -261.00 to 25.00, p = 0.11). Switching from bevacizumab/ranibizumab to aflibercept may improve persistent macular oedema secondary to RVO. However, there may be a limitation in the potential of visual recovery.

Ultra-Widefield Fluorescein Angiography as a Biomarker for Response to Switch in Therapy in Persistent DME.

BACKGROUND AND OBJECTIVE: To explore the effect of peripheral ischemia identified on ultra-widefield fluorescein angiography (UWFA) as a biomarker of response to a switch in therapy from bevacizumab to aflibercept in persistent diabetic macular edema (DME). PATIENTS AND METHODS: Prospective clinical trial of 38 eyes from 38 patients previously treated with bevacizumab and persistent DME. Patients subsequently received aflibercept per protocol and were followed up for 48 weeks. UWFA was obtained for all patients at baseline and 48 weeks. Images were graded and used to calculate an overall ischemic index (II) and macular ischemic index (MII). II was compared with visual and central macular thickness (CMT) outcomes. Paired and independent samples t-tests and Fisher's exact tests were used to assess change and associations. RESULTS: Patients with an II greater than or equal to 50% at baseline had a poorer baseline visual acuity (VA) (60.1 ± 10.2 vs. 70.7 ± 9.0 letters; P = .005) and a worse MII (6.9 ± 25 vs. 56 ± 52%; P < .001). These patients gained significantly more vision at 48 weeks (8.3 ± 9.3 vs. 2.6 ± 5.9 letters; P = .03). At 48 weeks, there was no significant difference in VA of patients with an II greater or less than 50% (68.4 ± 6.0 vs. 73.3 ± 9.6 letters; P = .16). CONCLUSIONS: Patients with persistent DME treated with bevacizumab and worse II had poorer baseline VA, potentially due to worse macular ischemia. These patients had greater visual gain with similar final visual outcomes of those without marked peripheral ischemia subsequent to switching to aflibercept. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:771-778.].