Validation of choroidal hyperreflective foci in diabetic macular edema through a retrospective pilot study

Purpose:Choroidal hyperreflective foci (HCF) are novel spectral-domain optical coherence tomography (SDOCT) biomarkers in diabetic macular edema (DME). The present study intended to validate HCF and assess their role in the treatment outcome.Methods:It was a retrospective, longitudinal, records-based pilot study recruiting consecutive patients of nonproliferative diabetic retinopathy with treatment naïve DME. Patients were treated with three intravitreal anti-vascular endothelial growth factor injections and followed by a pro re nata regimen.Results:A total of 43 eyes of 28 patients were included in the study. Eyes were divided into two groups. Group A (n = 19) comprised eyes with retinal hyperreflective foci (HRF) and group B (n = 24) had eyes with both HRF and HCF. The mean age of patients in group A and B was 58.5 ± 2.1 years and 55.2 ± 8.8 years, respectively. Mean best-corrected visual acuity at presentation was 0.38 ± 0.25 in group A and 0.59 ± 0.29 in group B (P = 0.01). Final BCVA was 0.35 ± 0.39 in group A and 0.47 ± 0.34 in group B (P = 0.3). External limiting membrane was intact in 19 out of 19 eyes in group A and two (8.3%) eyes in group B (P = 0).Conclusion:Presence of HCF meant significantly worse initial BCVA compared to the eye that had HRF alone. The final BCVA was also worse in eyes with HCF compared to those with HRF and without HCF; however, the difference did not reach a significance level, probably pointing toward the fact that HCF and HRF are pathophysiologically identical. Further studies with a larger sample size and prospective design are needed to take these findings forward.     

Profile of patients receiving intravitreal anti-vascular endothelial growth factor injections during COVID-19-related lockdown

Purpose:The aim of this study was to analyze the impact on vision due to delay in presentation of patients requiring intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, consequent to COVID-19-related travel restrictions.Methods:Data were collected retrospectively of patients who received anti-VEGF injections during four months of the COVID-19 pandemic. Visual acuities, indication for treatment were noted along with basic demographic characteristics.Results:Data were analyzed for 303 eyes of 263 patients. The indication for treatment was age-related macular degeneration (AMD) in 60 eyes (19.8%), while 162 eyes (53.5%) had Diabetic Macular Edema, 71 eyes (23.4%) had Retinal Vein Occlusion and 10 eyes (3.3%) had other diagnosis. The visual acuity in the treatment naïve eyes (Group A, n = 168) was significantly worse (P < 0.001) than those who presented for retreatment (Group B, n = 135). In Group B, there was a significant decline in vision for the entire cohort (P = 0.009) and those with AMD (P = 0.036). Those in Group B presented at a mean interval of 19.1 ± 10.6 (range, 4–64) weeks for retreatment.Conclusion:The COVID-19 pandemic has led to a delay in patients receiving anti-VEGF injections. The visual acuity is worse in both treatment naïve as well as those requiring retreatment. This could have long-term impact on vision of patients requiring this vision preserving treatment.     

Comparison of anatomical and functional outcomes of vitrectomy with internal limiting membrane peeling in recalcitrant diabetic macular edema with and without traction in Indian patients

Purpose:To study and compare the outcomes of pars plana vitrectomy (PPV) with the internal limiting membrane (ILM) peeling in the eyes with recalcitrant diabetic macular edema (DME) with and without vitreomacular traction.Methods:A comparative prospective interventional study was undertaken in which group 1 included 45 eyes of 45 patients with DME with vitreomacular tractional component and group 2 included 45 eyes of 45 patients with recalcitrant DME without a tractional component. Both groups underwent standard PPV with ILM peeling. All the patients were followed up for a minimum of 6 months. The parameters evaluated were changes in the best-corrected visual acuity (BCVA), central macular thickness (CMT), multifocal electroretinogram (mfERG) parameters, and occurrence of any intraoperative/postoperative surgical complication.Results:The mean CMT improved significantly from 540.6 and 490.2 μm at the baseline to 292.5 and 270.6 μm at 6 months in groups 1 and 2, respectively (P < 0.001). The mean BCVA logMAR improved from 0.78 ± 0.21 to 0.62 ± 0.22 in group 1 and 0.84 ± 0.19 to 0.65 ± 0.21 in group 2 at 6 months follow-up which was not statistically significant. The improvement in the mfERG was seen in group 2 as a significant increase in P1 wave amplitude in ring 2 (2–5°) (P < 0.004) and a significant decrease in P 1 wave implicit time in ring 1 (central 2°) (P < 0.001). None of the eyes suffered from the loss of BCVA or any major surgical complication in either group.Conclusion:PPV in recalcitrant DME provides good anatomical outcomes and the results are comparable in DME with and without a tractional component.     

Correlation between retinal sensitivity and cystoid space characteristics in diabetic macular edema

Purpose:To evaluate the correlation between retinal sensitivity and cystoid space characteristics in eyes with diabetic macular edema (DME).Results:Subject''s mean age was 57 ± 9 years. The mean logarithm of minimum angle of resolution BCVA was 0.4 ± 0.2. The intraclass correlation coefficient for inter- and intra-grader assessment of cystoid space volume by manual delineation was 0.99 and 0.99, respectively. Mean total ICS volume was 0.4 ± 0.4 mm³ and for the foveal center, subfield was 0.1 ± 0.1 mm³. Mean retinal sensitivity was 12.89 ± 10 dB; however, foveal retinal sensitivity was 12.3 ± 11.1 dB. We found no significant correlation between BCVA and total cystoid space volume (r = 0.33, P = 0.06). Correlation between total retinal sensitivity and total ICS was negative and nonsignificant (r = −0.17, P = 0.36). Correlation between foveal retinal sensitivity and foveal cystoid space intensity was moderate and marginally significant (r = −0.43, P = 0.05).Conclusion:Total cystoid space volume was not significantly correlated with BCVA or total retinal sensitivity in subjects with DME. Foveal cystoid space optical intensity was negatively correlated with foveal retinal sensitivity. These findings suggest further investigation of cystoid space characteristics in the setting of DME may be of value.     

One-year outcomes of Aflibercept for refractory diabetic macular edema in Bevacizumab nonresponders

Purpose:A sub-population of patients with diabetic macular edema (DME) responds less effectively to off-label use of Bevacizumab. Approval of Aflibercept for DME has offered Bevacizumab nonresponders an alternative therapeutic option. Herein, we investigate the anatomical and functional changes associated with Aflibercept treatment in Bevacizumab nonresponders with chronic DME in a Canadian setting.Methods:A retrospective study of eyes with persistent DME that were switched to Aflibercept due to nonresponse following ≥6 consecutive monthly Bevacizumab injections was performed. Anatomical and functional changes and the predictors of response were assessed using patients'' characteristics prior to receiving their first (baseline) and seventh consecutive Aflibercept injections (follow-up).Results:Twenty-four eyes were included, with a mean age of 63.9 ± 10.7 years, an average of 16.8 ± 8.5 Bevacizumab injections prior to switching to Aflibercept, and mean follow-up duration of 11.8 ± 1.7 months following switching to Aflibercept. Best-corrected visual acuity (BCVA) improved significantly from 0.49 ± 0.13 to 0.41 ± 0.11 logMAR (P < 0.001) and central subfield thickness (CST) decreased by 119.4 μm from 409.4 ± 85.8 μm to 290.0 ± 64.5 μm (P < 0.001), with 50% of eyes showing complete anatomical response. Worse BCVA and higher CST at baseline predicted greater vision improvements (P = 0.001 and P = 0.035, respectively) while a larger decrease in CST was associated with greater baseline CST (P = 0.001) and better glycemic control (P = 0.039).Conclusion:Our data from a real-world clinical setting highlight the efficacy of Aflibercept as an alternative therapeutic option for DME recalcitrant to Bevacizumab, with potential additional benefit to those with worse vision, greater CST, and better glycemic control at baseline.     

Topical interferon therapy in uveitic macular edema

Purpose:To evaluate efficacy of topical interferon alfa-2b (IFN) in the treatment of uveitic macular edema (UME).Methods:This is a prospective, interventional case study of patients with UME. Injection IFN was reconstituted into eye drops and a four times/day (QID) application was prescribed. Central macular thickness (CMT) on optical coherence tomography (OCT) scan was evaluated. Improvement in CMT by ≥50 mm from the baseline was studied in eyes with presenting CMT ≥400 µm.Results:Twenty eyes of 20 patients with UME were studied: anterior uveitis (n = 3), anterior + intermediate uveitis (n = 5), posterior uveitis (n = 3), retinal vasculitis (n = 3), and panuveitis (n = 6). Mean CMT at the presentation was 423.3 µm (range: 270–604 µm), which improved at 1 month (n = 16), 2 months (n = 10), and ≥3 months (n = 11) follow-up, to 415.3 µm (range: 247–579 mm) (P = 0.411), 364.4 mm (range: 258–566 µm) (P = 0.099), 344 µm (range: 258–484 µm) (P = 0.001), respectively. Twelve eyes of 12 patients had presenting CMT ≥400 µm. In these cases, decrease in CMT by ≥50 µm was seen in 4/10, 4/5, and 5/6 eyes at 1 and 2 months and ≥3 months follow-up. Mean follow-up was 4 months (range: 1–17 months). Complete resolution of UME was seen only in three eyes. No ocular or systemic side effects were observed.Conclusion:Topical IFN therapy in QID doses is safe but may have limited role in UME. Long-term therapy may improve its efficacy. Larger studies with dose modification, combination with other drugs, and with homogeneous uveitis population are recommended.     

Impact of treatment of diabetic macular edema on visual impairment in people with diabetes mellitus in India

Purpose:The aim of this study was to report visual and anatomical outcomes following treatment for diabetic macular edema (DME) in clinical practice in India.Methods:Retrospective chart review of patients with DME who were initiated on treatment and followed up for at least 1 year at 9 tertiary eye care centers during 2016–2017 was performed. Data on demographics, systemic illnesses, visual acuity and anatomical characteristics of DME, treatment history were collated and analyzed for change in visual acuity level and central macular thickness at 1 year.Results:A total 1853 patients were diagnosed with treatable DME during study period, 1315 patients were treated and 556 patients (1019 eyes) followed up at one year. Although patients achieved significantly better anatomical outcome (central macular thickness of <300μ in 32.3% at baseline compared to 60.7% at 1 year, P < 0.001), visual impairment due to DME did not differ from baseline (mild visual impairment in 53.2% at baseline compared to 56% at 1 year, P = 0.7). Cystoid type of DME was the most common phenotype (432/1019, 42.4%) followed by spongy type (325, 31.9%) and cystoid plus spongy type (138, 13.5%). Bevacizumab monotherapy was the most common (388/1019, 38.1%) treatment followed by combination therapy (359, 35.2%). Mean number of anti-VEGF injections received per eye in a year was 2.1 (SD ± 0.9).Conclusion:Only about a third of treated DME patients complete one year follow up in India. Most patients receive suboptimal number of treatments. Treated DME cases largely show better anatomical outcome but not a better functional outcome.     

Initial experience in treating polypoidal choroidal vasculopathy with brolucizumab in Indian eyes – A multicenter retrospective study

Purpose:To report the initial experience of managing treatment-resistant and treatment-naïve eyes with polypoidal choroidal vasculopathy (PCV) by using brolucizumab 6 mg.Methods:This was a retrospective multicentric series of all consecutive eyes with PCV treated with brolucizumab. Treatment resistance was defined as taking at least six prior anti-VEGF injections over the past 1 year and showing persistent disease activity in the form of intra (IRF) or subretinal fluid (SRF) or both. All patients were treated on a pro re nata (PRN) basis and followed up monthly. Retreatment was considered when either SRF or IRF were present at any time point during the study.Results:We included 21 eyes of 21 patients with PCV with a mean age of 65.1 ± 9.9 years, of which 16 eyes (76%) were treatment-resistant. The mean follow-up period from receiving the first brolucizumab was 27.3 ± 3.3 weeks. Of the 21 eyes, seven eyes (33%) received three injections during follow-up, 13 eyes (62%) received two injections, and one eye received one injection. The mean injection-free interval was 12 ± 1.2 weeks. The median pretreatment vision was 0.6 logMAR (IQR = 0.47–1 logMAR) and improved to 0.3 logMAR (IQR = 0.25–0.6 logMAR), whereas the mean macular thickness improved from 443 ± 60 mm at baseline to 289 ± 25 mm (P < 0.001) at the last follow-up period. None of the eyes experienced any intraocular inflammation across 48 injection sessionsConclusion:Brolucizumab is safe and effective in controlling PCV disease in both treatment-resistant and treatment-naïve eyes.     

Surgical outcome of full-thickness macular hole secondary to tractional retinal detachment in proliferative diabetic retinopathy

Purpose:To evaluate the surgical outcome of full-thickness macular hole (FTMH) secondary to active fibrovascular proliferation (FVP) and tractional retinal detachment (TRD) in eyes with proliferative diabetic retinopathy (PDR), and factors influencing the outcome.Methods:This retrospective study included the patients who underwent vitrectomy for FTMH secondary to PDR TRD from 2016 to 2020. Anatomical and visual outcomes were analyzed after six months along with the factors predicting the final outcome and duration of subretinal fluid (SRF) resolution.Results:Group A (macula-off combined RD, i.e., tractional and rhegmatogenous) included 10 eyes, while group B (macula-threatening TRD) included eight eyes. The mean best-corrected visual acuity improved from logMAR 1.21 (Snellen equivalent: 20/324) to logMAR 0.76 (Snellen equivalent: 20/115) (P = 0.008). Seventeen patients gained ≥1 line(s) of vision. Mean visual gain in groups A and B was 3.7 ± 1.9 and 1.9 ± 1.1 lines, respectively (P = 0.051). MH closed in 88.9% eyes. Type 1 anatomical closure was achieved in 88.9% of eyes. At 6 months, SRF and central macular thickness reduced from 479.6 ± 512.5 μm to 11.4 ± 23.5 μm (P = 0.002) and 874.3 ± 422.6 μm to 207.6 ± 81.7 μm (P = 0.0002), respectively. Finally, macular SRF resolved in all the patients. The mean duration for complete SRF resolution was 4.9 ± 3.2 months. Eyes with a shorter duration of diabetes mellitus (rho = −0.49, P = 0.040) and macula-off combined RD (P = 0.048) took a longer time for complete SRF resolution.Conclusion:Good anatomical and visual outcomes can be achieved in eyes with PDR TRD-associated FTMH. The residual macular SRF resolves slowly after the surgery and extra intervention is not required. Macula-off combined RD is associated with worse outcome and a slower SRF resolution rate.     

Intraocular soluble intracellular adhesion molecule-1 correlates with subretinal fluid height of diabetic macular edema

Objective:

To investigate the correlations between aqueous concentrations of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and diabetic macular edema (DME).

Materials and Methods:

VEGF, MCP-1 and sICAM-1 concentrations in aqueous humor samples of 22 patients with DME and 23 patients with cataract of a control group were measured with solid-phase chemiluminescence immunoassay.

Results:

Aqueous VEGF (89.2 ± 58.5 pg/ml versus 48.5 ± 27.8 pg/ml, P = 0.006), MCP-1 (684.2 ± 423.4 pg/ml versus 432.4 ± 230.4 pg/ml, P = 0.019) and sICAM-1 (3213.8 ± 2581.6 pg/ml versus 260.2 ± 212.2 pg/ml, P < 0.001) all vary significantly between DME group and control group. Maximum height of submacular fluid measured by Optical coherence tomography (OCT) was significantly associated with aqueous sICAM-1 (r = -0.45, P = 0.034). The maximum height of macular thickness measured by OCT was not significantly associated with either VEGF (P = 0.300), MCP-1 (P = 0.320) or sICAM-1 (P = 0.285).

Conclusions:

Our results suggest that sICAM-1 may majorly contribute to the formation of subretinal fluid in DME patients and imply that MCP-1 and sICAM-1 may be the potential therapy targets, besides VEGF.     

Clinical efficacy and safety of Razumab® (CESAR) study: Our experience with the world's first biosimilar Ranibizumab

Purpose:The aim of this study was to evaluate the efficacy and safety of Razumab (the biosimilar Ranibizumab by Intas Pharmaceuticals Ltd.) for the treatment of chorioretinal vascular diseases such as diabetic macular edema (DME), choroidal neovascular membrane (CNVM), and macular edema secondary to retinal vein occlusion (RVO).Methods:We conducted a single-center, retrospective study, including patients with DME, CNVM, and RVO, who had received treatment with Razumab® between October 2018 and September 2019. Primary outcome measures were the changes in corrected distance visual acuity (CDVA) and central foveal thickness (CFT) from baseline to 1 month and 3 months. Secondary outcome measures included intraocular pressure (IOP) at day 1, any signs of ocular inflammation or systemic adverse events during the follow-up.Results:One hundred and fifty-three eyes of 141 patients were analyzed. The indications included DME in 70 (45.8%) eyes, CNVM in 70 (45.8%) eyes, and RVO in 13 (8.4%) eyes. Mean CDVA improved from baseline (0.62 ± 0.44) to month 1 (0.45 ± 0.42) and maintained till 3 months (0.42 ± 0.44; P < 0.001). Mean CFT showed significant reduction from baseline (405.68 ± 192.422 μm) to month 1 (286.08 ± 118.36 μm) and month 3 (271 ± 104.24 μm; P < 0.001). None of the eyes recorded IOP >20 mmHg on day 1. No evidence of ocular toxicity or systemic adverse event was noted.Conclusion:Razumab® showed a rapid improvement in CDVA and CFT in most of the eyes with efficacy observed as early as 1 month and maintained till 3 months. The biosimilar Ranibizumab can be a safe and effective low-cost drug for treating macular diseases.     

Anatomic–Functional Correlates in Lesions of Retinal Vein Occlusion

PurposeTo evaluate anatomic–functional associations at sites of retinal lesions in retinal vein occlusion (RVO).MethodsThis pilot, prospective, observational study was conducted at the Northern Ireland Clinical Research Facility (NICRF) of Queen''s University and the Belfast Health and Social Care Trust, Northern Ireland, between August 1, 2018, and September 30, 2019. The study included 10 treatment-naïve patients with RVO (10 RVO eyes and 10 fellow eyes). There were 81 points/sites assessed for each eye at baseline; six patients were re-assessed 6 months after anti-vascular endothelial growth factor therapy at the same locations. We investigated associations between retinal sensitivity and presence of structural RVO lesions, including retinal ischemia, hemorrhages, intraretinal fluid (IRF) and subretinal fluid outside the foveal/parafoveal regions. Comparisons were made between RVO eyes and fellow eyes at baseline, and between RVO eyes at baseline and at 6 months after treatment. Regression models were used to investigate anatomic–functional associations.ResultsAt baseline, strong associations were found between reduced retinal sensitivity and presence of ischemia (estimate = −2.08 dB; P < 0.001), intraretinal fluid (estimate = −7.82 dB; P < 0.001), and subretinal fluid (estimate = −8.66 dB; P < 0.001). Resolution of subretinal fluid but not intraretinal fluid was associated with improved function (estimate = 2.40 dB [P = 0.022]; estimate = 1.16 dB [P = 0.228], respectively). However, reperfusion of ischemic retina, observed in 31 of 486 points (6%) 6 months after anti-vascular endothelial growth factor therapy, was associated with a further decrease in retinal sensitivity (estimate = −2.34 dB; P = 0.035).ConclusionsRetinal sensitivity was decreased at sites of RVO lesions. Decreased function at sites of retinal ischemia did not recover after treatment, even when reperfusion occurred.     

The Association of Fluid Volatility With Subretinal Hyperreflective Material and Ellipsoid Zone Integrity in Neovascular AMD

PurposeTo evaluate the association of fluid volatility with ellipsoid zone (EZ) integrity and subretinal hyperreflective material (SHRM) volume during anti–vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (nAMD).MethodsThis study was a post hoc analysis of the OSPREY study. Retinal volatility was quantified as the standard deviation across weeks 12 to 56 for six optical coherence tomography (OCT) metrics: central subfield thickness (CST), total fluid (TF) volume, subretinal fluid (SRF) volume, intraretinal fluid (IRF) volume, macular total retinal fluid index (TRFI), and central macular TRFI. Eyes with volatility ≤ 25th or ≥ 75th percentile values were compared.ResultsEyes with low volatility in several exudative metrics showed greater change from baseline in SHRM volume at week 12 than eyes with high volatility. During the maintenance phase (weeks 12–56), eyes exhibiting high SRF volatility demonstrated increased SHRM volume compared to eyes with low SRF volatility (P = 0.027). Eyes exhibiting high volatility in CST, TF, and SRF demonstrated less improvement in EZ total attenuation (P < 0.001, P = 0.033, and P = 0.043, respectively) than eyes with low volatility. Early exudative instability (i.e., between weeks 4–8 or weeks 8–12) in multiple parameters (i.e., CST, TF, IRF, macular TRFI, or central macular TRFI) was associated with greater volatility during the maintenance phase (P < 0.05).ConclusionsGreater volatility in exudative OCT metrics, particularly SRF volatility, was associated with a greater increase in SHRM and less improvement in EZ integrity, suggesting that volatility is detrimental to multiple anatomic features in nAMD. Early exudative instability during the loading phase of treatment was associated with longer-term volatility in exudation.     

Progressive Dysmorphia of Retinal Pigment Epithelium in Age-Related Macular Degeneration Investigated by Fluorescence Lifetime Imaging

PurposeThe purpose of this study was to observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age-related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO).MethodsMultimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization (mean age = 74.2 ± 7.0 years). Twenty-three eyes were followed for 28.3 ± 18.3 months. Seven eyes had a second follow-up after 46.6 ± 9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, hyper-reflective foci (HRF) on OCT, attributed to single or clustered intraretinal RPE, were identified. Fluorescence lifetimes in two spectral channels (short-wavelength spectral channel [SSC] = 500–560 nm, long-wavelength spectral channel [LSC] = 560–720 nm) as well as emission spectrum intensity ratio (ESIR) of the lesions were measured by FLIO.ResultsAs hyperpigmented areas form and RPE migrates into the retina, FAF lifetimes lengthen and ESRI of RPE cells increase. Thickened RPE showed lifetimes of 256 ± 49 ps (SSC) and 336 ± 35 ps (LSC) and an ESIR of 0.552 ± 0.079. For hyperpigmentation, these values were 317 ± 68 ps (p < 0.001), 377 ± 56 ps (P < 0.001), and 0.609 ± 0.081 (P = 0.001), respectively, and for HRF 337 ± 79 ps (P < 0.001), 414 ± 50 ps (P < 0.001), and 0.654 ± 0.075 (P < 0.001).ConclusionsIn the process of RPE degeneration, comprising different steps of dysmorphia, hyperpigmentation, and migration, lengthening of FAF lifetimes and a hypsochromic shift of emission spectra can be observed by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.     

Postoperative microstructural re-modelling and functional outcomes in idiopathic full thickness macular hole

Purpose:To analyze the effect of various macular hole indices and postoperative microstructural changes of all retinal layers on postoperative functional outcomes in patients with idiopathic full-thickness macular hole (FTMH).Methods:In this prospective study, pre and post-operative optical coherence tomography (OCT) scans of 36 eyes with idiopathic FTMH were analyzed. Hole indices and microstructural changes of all retinal layers such as ellipsoid zone (EZ), external limiting membrane (ELM) integrity, outer and inner retinal defects, and cystoid resolution were studied on follow-up visits.Results:Out of 36 eyes, type-1 closure was achieved in 23 eyes (65.7%) and type-2 closure in 11 eyes (31.42%), one eye showed persistent hole, and one eye was lost to follow-up. The mean minimum diameter of hole (P = 0.026), mean MHI (P = 0.001), DHI (P = 0.158), THI (P = 0.001), and HFF (P < 0.001) showed statistical significance with the type of hole closure. Postoperatively, eyes with intact ELM and EZ had better BCVA at the final visit. The BCVA was better by logMAR 0.73 ± 0.38 (P < 0.001) in patients with absent outer retinal defects. There was a significant difference in BCVA of 0.52 ± 0.35 at 1 month and 0.64 ± 0.34 at 6 months in eyes without inner retinal defects (P < 0.001). At 6 months, cystoid resolution was observed in 28 (80%) eyes. BCVA was significantly better at 1 month (P < 0.001) and at 6 months (P = 0.001) in eyes with no DONFL.Conclusion:Macular hole indices determine the closure type. Postoperative regeneration of outer retinal layers and resolution of retinal defects significantly influence the final visual outcomes. ELM recovery is seen as a prerequisite for EZ regeneration with no new IRD after a period of 3 months.     

Outcomes of preoperative bevacizumab in diabetics with nonclearing vitreous hemorrhage without tractional detachment – A quasi-randomized retrospective study

Purpose:To assess whether preoperative bevacizumab (BVZ) in treatment-naïve eyes with proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH) without tractional retinal detachment (TRD) leads to lesser macular edema and better visual outcome compared to eyes that do not receive BVZ.Methods:This quasi-randomized retrospective study included 217 treatment-naïve eyes with nonclearing VH without TRD that had vitrectomy with or without BVZ and had a minimum 6-months follow-up. Postoperative variables, including visual acuity (BCVA), central macular thickness (CMT) at 1 month, and need for additional anti-VEGF injections till 6 months follow-up, were recorded for analysis.Results:Of the 217 eyes, 107 eyes (49%) received preoperative BVZ and 110 (51%) did not. Groups were comparable in terms of preoperative characteristics. At 1 month, mean CMT was significantly higher in eyes without BVZ (310 ± 33 μ vs. 246 ± 34μ; P < 0.001). The likelihood of developing center-involving DME at 1 month after vitrectomy was 67% lower if the eye received preoperative BVZ (OR = 0.33, 95%CI = 0.18–2.54, P = 0.56). Though BCVA improved significantly in both groups at 1 month, it was 1/3^rd of a line better in the BVZ group (β coefficient = −0.035 logMAR, 95%CI = −0.04 to −0.008 logMAR, P = 0.01).Conclusion:Preoperative BVZ in treatment-naïve eyes with PDR and VH but without TRD lead to better macular status and marginally improved vision at 1 month, which was maintained at 6 months. In view of these results, patients may be offered BVZ only when it is readily affordable to them.     

Comparison of two protocols of subthreshold micropulse yellow laser treatment for non-resolving central serous chorioretinopathy

Purpose:To study the effect of subthreshold micropulse yellow laser treatment on central serous chorioretinopathy (CSC) and to compare two laser protocols. As per our knowledge, there are no studies comparing the two protocols of subthreshold laser.Methods:Twenty-three patients with non-resolving CSC of at least three months duration were treated with subthreshold laser (577 nm). Ten patients were treated with 5% duty cycle (group A) and 13 patients with 10% duty cycle (group B). At one month, best corrected visual acuity (BCVA), central macular thickness (CMT), subretinal fluid (SRF), choroidal thickness (CT) and choroidal vascularity index (CVI) were evaluated.Results:In group A, BCVA improved from 0.508 ± 504 to 0.174 ± 0.171 (P = 0.0058), CMT improved from 349.8 ± 168.9 micrometers (µm) to 183.3 ± 70.312 µm (P = 0.0093) and SRF reduced from 202.4 ± 158.024 to 43.8 ± 46.599 µm (P = 0.0069). In group B, BCVA improved from 0.437 ± 0.426 to 0.289 ± 0.470 (P = 0.0026), CMT improved from 280.846 ± 72.668 to 196.769 ± 72.62 µm (P = 0.0002) and SRF reduced from 110.385 ± 57.687 µm to 52.538 ± 52.111 µm (P = 0.0064). No significant difference was found in BCVA and CMT between the groups (P = 0.8716 and P = 0.8523, respectively). CSC completely resolved in 50% of cases in group A and in 69.2% of cases in group B. This difference was not statistically significant (0.423); however, the odds ratio of resolution was 2.25 times more with 10% duty cycle. No change was observed on fundus autofluorescence (FAF) following laser.Conclusion:Subthreshold micropulse laser can lead to resolution of SRF in 60.87% of cases (groups A and B combined). Ten per cent duty cycle had higher odds of resolution without causing any RPE damage.     

Long-term efficacy of dexamethasone intravitreal implant in the treatment of Vogt-Koyanagi-Harada disease relapsing posterior uveitis

Purpose:To investigate the efficacy and safety of dexamethasone intravitreal implant in the treatment of relapsing posterior uveitis in patients with chronic recurrent Vogt–Koyanagi–Harada (VKH) disease.Methods: This was a prospective study of 29 eyes of 16 patients with posterior uveitis in chronic recurrent VKH disease. All patients received previous systemic steroid and immunosuppressive regimens. All patients underwent a comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), Indocyanine green angiography (ICGA), fundus fluorescein angiography (FFA), and spectral-domain optical coherence tomography (SD-OCT). All patients underwent intravitreal injection with sustained-release dexamethasone 0.7 mg implant (Ozurdex®). Primary outcome measures included mean change in BCVA and central foveal thickness (CFT) at 24 months of follow-up compared to the baseline.Results: At 24 month of follow-up, the mean BCVA improved from 0.82 ± 0.13 to 0.38 ± 0.06 logMAR (P < 0.0001). The mean CFT reduced from 505 ± 29 to 244 ± 23 um (P < 0.0001). The mean intraocular pressure (IOP) changed from 15.1 ± 2.2 to 16.9 ± 3.1 mmHg with no significant value (P-value = 0.0955). Twenty-one eyes (72.4%) received one injection, whereas eight eyes (27.6%) required two injections. The mean number of injections was 1.2 ± 0.60. The mean follow-up time was 24.75 ± 0.9 months. No serious ocular or systemic adverse events were noted during the follow-up period. Ocular hypertension was recorded in three (10.3%) eyes and controlled by IOP lowering medications. Cataract progression occurred in 11 (37.9%) eyes.Conclusion: Our cohort highlights the beneficial effects of the dexamethasone implant of 0.7 mg in the treatment of VKH disease relapsing posterior uveitis improving visual acuity, reducing macular edema, and minimizing the burden of systemic steroids in this sample study.     

Localized Structural and Functional Deficits in a Nonhuman Primate Model of Outer Retinal Atrophy

PurposeCell-based therapy development for geographic atrophy (GA) in age-related macular degeneration (AMD) is hampered by the paucity of models of localized photoreceptor and retinal pigment epithelium (RPE) degeneration. We aimed to characterize the structural and functional deficits in a laser-induced nonhuman primate model, including an analysis of the choroid.MethodsMacular laser photocoagulation was applied in four macaques. Fundus photography, optical coherence tomography (OCT), dye angiography, and OCT-angiography were conducted over 4.5 months, with histological correlation. Longitudinal changes in spatially resolved macular dysfunction were measured using multifocal electroretinography (MFERG).ResultsLesion features, depending on laser settings, included photoreceptor layer degeneration, inner retinal sparing, skip lesions, RPE elevation, and neovascularization. The intralesional choroid was degenerated. The normalized mean MFERG amplitude within lesions was consistently lower than control regions (0.94 ± 0.35 vs. 1.10 ± 0.27, P = 0.032 at month 1, 0.67 ± 0.22 vs. 0.83 ± 0.15, P = 0.0002 at month 2, and 0.97 ± 0.31 vs. 1.20 ± 0.21, P < 0.0001 at month 3.5). The intertest variation of mean MFERG amplitudes in rings 1 to 5 ranged from 13.0% to 26.0% in normal eyes.ConclusionsLaser application in this model caused localized outer retinal, RPE, and choriocapillaris loss. Localized dysfunction was apparent by MFERG in the first month after lesion induction. Correlative structure-function testing may be useful for research on the functional effects of stem cell–based therapy for GA. MFERG amplitude data should be interpreted in the context of relatively high intertest variability of the rings that correspond to the central macula. Sustained choroidal insufficiency may limit long-term subretinal graft viability in this model.     

Comparison of broadband and monochromatic photopic negative response in eyes of patients with diabetes with no diabetic retinopathy and different stages of diabetic retinopathy

Purpose:To evaluate the change in broadband (W/W), red on blue (R/B), and blue on yellow (B/Y) photopic negative response (PhNR) in patients with diabetes mellitus with no diabetic retinopathy (no DR) and different stages of DR and compare it with age-matched controls. This study was performed to provide a single PhNR protocol that can be used for early diagnosis of DR.Methods:It was a cross-sectional case-control study done in a hospital setup. Patients with diabetes with no DR and different stages of DR with no other associated ocular pathologies were included. Age-matched controls with no retinal pathologies were also included for comparison. All subjects underwent detailed ophthalmic examination and W/W, R/B, and B/Y electroretinography. Fifty control eyes and 52 treatment naïve eyes of 52 patients with diabetes [no DR = 11, mild nonproliferative diabetic retinopathy (NPDR) =11, moderate NPDR = 10, severe NPDR = 9, and proliferative DR = 11] were included in the study.Results:On comparing the ERG responses in patients with diabetes and age-matched controls, a significant reduction (P < 0.05) was noted in the amplitudes of a-wave (39.78 ± 11.34 μV vs. 67.28 ± 12.88 μV), b-wave (116.25 ± 45.25 vs. 134.39 ± 28.78 μV), W/W PhNR (33.86 ± 17.33 vs. 67.18 ± 15.99 μV), R/B PhNR (28.77 ± 15.85 vs. 53.48 ± 14.15 μV), and B/Y PhNR (55.04 ± 32.63 vs. 104.79 ± 24.37 μV). Post hoc analysis revealed that all the eyes in the diabetic group, including those with no DR, had a significantly reduced PhNR amplitude (P < 0.05) when compared with controls. PhNR was found to reduce in amplitude with increasing severity of DR (P < 0.05), with more significance in B/Y. Receiver operating characteristic showed highest area under the curve in B/Y PhNR (94%, P < 0.001), with maximum sensitivity and specificity of 88% and 87%, respectively.Conclusion:Changes in the amplitude and implicit time of ERG can reflect the severity of DR. PhNR amplitudes, especially B/Y PhNR, appear to be significantly reduced even in eyes with no DR.