Brolucizumab in Neovascular Age-Related Macular Degeneration - Indian Real-World Experience: The BRAILLE Study - Fifty-Two-Week Outcomes.

Purpose: To report the 52-week real-world efficacy and safety outcomes of brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in Indian eyes. Patients and Methods: A retrospective, multicentre chart analysis of 82 eyes of 82 patients with nAMD (switch therapy: 65 eyes; treatment-naïve: 17 eyes) with 52-week follow-up data was performed. Pro-re-nata re-treatment was offered based on visual and tomographic criteria. Changes in best-corrected visual acuity (BCVA), intraretinal fluid (IRF), subretinal fluid (SRF), central-subfield thickness (CST), and pigment epithelial detachment (PED) were the key outcome measures, coupled with the safety profile. Results: The mean age of the study population was 67.65 (±10.67) years, with 57 male patients (69.5%). The study's mean number of injections was 4.8 (± 0.77). After brolucizumab therapy, the BCVA improved significantly at weeks 4 (P<0.001), and maintained up to week 52 (P<0.001). The CST also reduced significantly at all the visits (Baseline: 413.6 ± 64.6 µm; 52-week: 292.37 ± 13.5 µm; P<0.001). Significantly fewer eyes demonstrated residual SRF (P<0.001) and IRF (P<0.001) at all visits, starting with week 12 and continuing until week 52. The PED resolution was significant from week 24 through week 52 (P=0.004). Each of the 82 eyes received four injections of brolucizumab, with 63.4% (52 eyes) receiving a fifth dose and only 17.1% requiring a sixth. Mild intraocular inflammation (IOI) was seen in three eyes (3.66%) that resolved conservatively. One patient (1.2%) developed mild fever that subsided with oral medications. Conclusion: The 52-week BRAILLE study demonstrates that brolucizumab is effective and safe in nAMD eyes in a real-world setting. Brolucizumab treatment can reduce the therapeutic burden in patients with nAMD due to its rapid, sustained efficacy and favourable safety profile.

Rapid Onset Neovascular Glaucoma due to COVID-19-related Retinopathy.

Aim: To present a case of rapid onset on neovascular glaucoma following the Coronavirus disease 2019 (COVID-19). Background: COVID-19 has various ocular manifestations such as conjunctivitis, uveitis, retinal vasculitis, and so on. However, to date, the development of neovascular glaucoma has not been reported in COVID-19. Case description: A 50-year-old male with a history of COVID-19 3 weeks ago presented with left eye (OS) central retinal artery occlusion (CRAO) and right eye (OD) cystoid macular edema with disc and microvascular leakage on multimodal imaging. After being managed conservatively for 2 weeks, the patient developed OD neovascular glaucoma with intraocular pressure (IOP) of 44 mm Hg and angle neovascularization (NVA) on gonioscopy. The patient was started on topical antiglaucoma medications (AGM) with panretinal photocoagulation (PRP) and responded well with complete regression of NVA, CME, and normal IOP after 3 weeks. Conclusion: This is the first reported case of rapid onset of NVG secondary to COVID-19-induced retinal vasculitis. COVID-19-associated prothrombotic state with secondary retinal vascular involvement can potentially trigger such NVG. Such NVG responds well with topical AGM and PRP therapy. Clinical significance: Given the global COVID-19 pandemic, it is imperative to be vigilant regarding the various vision-threatening manifestations associated with the disease such as the NVG. How to cite this article: Soman M, Indurkar A, George T, et al. Rapid onset Neovascular Glaucoma due to COVID-19-related Retinopathy. J Curr Glaucoma Pract 2022;16(2):136-140.

Updated guidelines for the management of polypoidal choroidal vasculopathy: Recommendations from the Indian Polypoidal Choroidal Vasculopathy Panel and the Vitreoretinal Society of India.

In Asians, polypoidal choroidal vasculopathy (PCV) is becoming more widely recognized as a significant cause of exudative maculopathy. The previous set of Indian guidelines on the management of PCV were published in 2018, with a literature search updated up to November 2015. As the treatment of PCV evolves, retinal physicians must constantly modify their current practice. The current guidelines are based on the most up-to-date information on PCV and are an update to the previous set of guidelines. These guidelines were developed by a panel of Indian retinal experts under the aegis of the Vitreoretinal Society of India (VRSI), based on a comprehensive search and assessment of literature up to September 2021. The final guidelines i) provide the updated nomenclature in PCV; ii) discusses the newer diagnostic imaging features of PCV, especially in the absence of indocyanine green angiography (ICGA); and iii) recommends the best possible therapeutic approach in the management of PCV, including the choice of anti-vascular endothelial growth factor (anti-VEGF) agents, treatment regimen, and the role of switching between the anti-VEGF agents. In the face of non-availability of photodynamic therapy (PDT) in India, we constructed practical recommendations on anti-VEGF monotherapy in PCV. The current updated recommendations would provide a broader framework to the treating retinal physician for the diagnosis and management of PCV for optimal therapeutic outcomes.

Innovator Versus Biosimilar Ranibizumab in Polypoidal Choroidal Vasculopathy: Real-World Evidence.

INTRODUCTION: To analyze the efficacy and safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab® (Intas Pharmaceuticals, Ahmedabad, India; BRm; Razumab®) and the innovator ranibizumab drug (IRm; LUCENTIS®) in Indian patients with polypoidal choroidal vasculopathy (PCV) under real-world conditions. METHODS: This was a retrospective study of treatment-naïve and previously treated PCV eyes undergoing intravitreal therapy with either BRm or IRm from January 2019 to September 2020 as three loading doses followed by a pro-re-nata (PRN) regimen. Changes in the best-corrected visual acuity (BCVA), subretinal fluid (SRF), intraretinal fluid (IRF), SRF height, and subfoveal choroidal thickness (SFCT) and the safety profiles were assessed at weeks 12, 24, and 52, respectively. RESULTS: A total of 22 eyes received IRm and 19 eyes underwent BRm therapy, respectively. Both the groups were comparable in age (P = 0.41) and gender distribution, although the BRm arm had significantly more eyes that were previously treated (P < 0.00001) with a greater median number of injections (P < 0.0001). At week 52, both groups had similar gains in visual acuity (P = 0.19), SRF resolution (P = 0.8), IRF resolution (P = 0.47), and SRF height (P = 0.71). The IRm eyes exhibited a significant improvement in BCVA (P = 0.001) at all visits with a greater mean number of injections (IRm: 5.41 ± 0.94; BRm: 4 ± 1.45; P = 0.0004), while the BRm eyes showed a similar increase in BCVA but did not reach statistical significance until week 52. The SFCT decreased significantly in the BRm arm at week 52 (P = 0.045). One eye (5.26%) in the BRm arm experienced mild anterior uveitis, which was treated with topical corticosteroids. In either arm, no other ocular or systemic adverse effects were observed. CONCLUSIONS: Our real-world data demonstrated the ranibizumab biosimilar Razumab to have comparable visual acuity outcomes to the innovator ranibizumab molecule with an adequate safety profile in the management of PCV. Although these encouraging results support its use as a viable alternative to the innovator molecule, further prospective studies in a diverse patient population are needed to validate our findings.

Role of intravitreal brolucizumab with intravitreal rtPA and pneumatic displacement for submacular hemorrhage: A case series.

PURPOSE: To evaluate the role of intravitreal injection (IVI) of brolucizumab along with intravitreal recombinant tissue plasminogen activator (rtPA) and C3F8 gas injection for large submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). OBSERVATIONS: This was a prospective uncontrolled non-randomized case series conducted at a single site. Three patients with fresh SMH (≤4 days) secondary to nAMD underwent triple therapy with IVI brolucizumab + intravitreal rtPA (50 µg in 0.1 mL) + 0.3 mL of 100% C3F8 gas injection. Post-injection, a face-down position was advised for 5 days with periodic follow-up visits. All three patients had complete resolution of SMH at the end of 4 weeks with a notable improvement in the best-corrected visual acuity (BCVA). No optical coherence tomographic (OCT) biomarkers of disease activity were noted at the end of 12 weeks in the first and the third case and 4 weeks in the second case respectively. There were no ocular or systemic side effects reported in any of the cases. CONCLUSIONS AND IMPORTANCE: Intravitreal brolucizumab administered along with intravitreal rtPA and C3F8 gas injection was found to be efficacious and safe for the management of large SMH secondary to nAMD. Complete displacement of SMH with excellent structural and functional outcomes can be seen with triple therapy.

Idiopathic lenticular surface neovascularization: An unusual presentation.

PURPOSE: To present a case of posterior lenticular surface neovascularization in the absence of any ocular or systemic pathology. OBSERVATIONS: A 29-year-old asymptomatic male was detected with the right eye (OD) posterior lenticular surface neovascularization extending for six-clock hours in the temporal portion along with the presence of mild posterior capsular haze. His best-corrected visual acuity was 20/25 in OD and 20/20 in the left eye (OS). No additional abnormality was identified in the remainder of the OD anterior segment and the fundus respectively. OS evaluation was unremarkable. OD imaging including B-scan ultrasonography and ultrasound biomicroscopy (UBM) were essentially normal. The anterior segment optical coherence tomography (AS-OCT) thickened lens capsule with a dense hyperreflective layer adhered to its posterior surface and separating from the capsule in the periphery. Few hyperreflective dots were visible posterior to the ciliary body although no CB thickening was noted. No systemic abnormality was detected. The patient is being managed conservatively and has shown no signs of progression of the neovascularization over six months. CONCLUSIONS AND IMPORTANCE: This is the first reported case of an isolated idiopathic posterior lenticular surface neovascularization occurring in an otherwise healthy patient. Although an unspecified breach in the posterior capsule or undetermined cyclitis can trigger such neovascularization, further histopathological studies of the capsular biopsy and ciliary body can provide better insight into its etiopathogenesis. Additionally, considering the asymptomatic nature of the condition, these patients can be observed and closely monitored.

Progression of Subclinical Pachychoroid Neovasculopathy to an Active Neovascularization in the Presence of Acquired Vitelliform Lesions.

We describe a unique case of bilateral acquired vitelliform lesions in a 67-year-old-female with pachychoroid associated with subretinal fluid in the right eye (OD) and a nonexudative choroidal neovascular membrane (CNVM) in the left eye (OS). Multimodal imaging performed at baseline and over the ensuing two years showed an increase in the OS vitelliform lesions with a concurrent transformation of quiescent CNVM to an exudative form. Further studies are warranted to gain better insight into the etiopathogenesis of these vitelliform lesions in pachychoroid and their potential role in instigating CNVM activation.

Off-label intravitreal brolucizumab for recalcitrant diabetic macular edema: A real-world case series.

PURPOSE: To report the efficacy of intravitreal injection (IVI) of brolucizumab for recalcitrant diabetic macular edema (DME) in a real-world setting. OBSERVATIONS: This was a single-center, prospective uncontrolled non-randomized case series. Three eyes with recalcitrant DME, who have received a minimum of ten intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, underwent IVI brolucizumab and were followed-up for minimum of 16 weeks. Patients underwent best-corrected visual acuity (BCVA) testing, ophthalmic examination, and optical coherence tomography at baseline and all the scheduled follow-up visits (Weeks 4, 8, 12, and 16). All three patients demonstrated notable improvement in BCVA and reduction in the fluid on SD-OCT lasting up to week 12. At week 16, all three eyes maintained the visual acuity gains. However, early increase in fluid was noted in all the three cases, for which second dose of IVI brolucizumab was planned. No ocular or systemic adverse events were noted in any of the cases. CONCLUSIONS AND IMPORTANCE: In this real-world case series, treatment with IVI brolucizumab exhibited excellent visual acuity outcomes lasting up to 16 weeks for the treatment of recalcitrant DME. Single dose IVI brolucizumab achieves good anatomical improvement based on SD-OCT persisting up to 12 weeks, followed by early recurrence of fluid at week 16. The results did not show any ocular or systemic safety concerns for IVI brolucizumab.

Brolucizumab in Neovascular Age-Related Macular Degeneration - Indian Real-World Experience: The BRAILLE Study.

PURPOSE: To assess the short-term efficacy and safety profile of intravitreal brolucizumab injection in Indian eyes with neovascular age-related macular degeneration (nAMD) under real-world conditions. PATIENTS AND METHODS: This was a multicenter, retrospective chart review of 94 eyes of 94 patients with nAMD (treatment-naïve and switch-therapy) undergoing brolucizumab therapy. Re-treatment as per pro-re-nata protocol was performed based on fixed visual and tomographic criteria. The main outcome measures were changes in the best-corrected visual acuity (BCVA), intraretinal fluid (IRF), subretinal fluid (SRF), central subfield thickness (CST), and pigment epithelial detachment (PED) along with safety analysis. RESULTS: Of the 94 eyes, 20 eyes (21.3%) were treatment-naïve, whereas the rest 74 eyes (78.7%) underwent switch therapy. One hundred and twenty-six injections were given over a mean follow-up of 7.3 ± 2.2 (range 5-30) weeks. The BCVA improved significantly from 0.82 ± 0.5 LogMAR at baseline to 0.66 ± 0.5 LogMAR at the final visit (p < 0.0001). Significant reduction in CST was simultaneously noted (Baseline: 408.45 ± 65.63 µm; Final: 281.14 ± 37.74 µm; p < 0.0001). On qualitative analysis, resolution of subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelial detachment (PED) was observed in 15.5%, 39.29%, and 23.81% of the eyes, respectively. The mean interval of repeat injection was 10.2 ± 2.1 weeks. Three episodes of ocular adverse drug reaction were reported, including two patients developing subretinal hemorrhage while one having a retinal pigment epithelial (RPE) tear. Notably, no intraocular inflammation (IOI) was seen in any of the eyes, and no systemic side effects were identified. CONCLUSION: In a real-world scenario, brolucizumab therapy is efficacious and safe in the management of nAMD over the short term. Further long-term studies are warranted to validate these findings. Additionally, lack of ocular inflammation after 126 brolucizumab injections in our Indian data is peculiar and underlines the necessity to explore the role of race and genetics in predisposing to/safeguarding against brolucizumab-related IOIs.

De-novo multilayering in fibrovascular pigment epithelial detachment.

This study describes the occurrence of multilayered pigment-epithelial detachment (MLPED) as a De-novo phenomenon (DN-MLPED) and compare the features with multi-layering secondary to chronic anti-vascular endothelial growth factor (anti-VEGF) therapy (s-MLPED). We did a retrospective evaluation of spectral-domain optical coherence tomography (SD-OCT) features, treatment-profile, and visual-acuity (VA) outcomes in eyes with MLPED. Out of 17 eyes with MLPED, 7 eyes had DN-MLPED and 10 eyes had s-MLPED. There was no significant difference in baseline and final VA between the groups. At the final visit, no significant visual improvement was noted in both the groups, although a possible trend towards an improvement was seen in DN-MLPED eyes while the s-MLPED demonstrated a declining trend (DN-MLPED-LogMAR-BCVA: Baseline = 0.79 [∼ 20/123] ± 0.91; Final = 0.76 [∼ 20/115] ± 0.73; p = 0.87; s-MLPED-LogMAR BCVA: Baseline = 0.43 [∼ 20/54] ± 0.68; Final = 0.94 [∼ 20/174] ± 0.71; p = 0.06). Moreover, after presentation, the median number of injections in DN-MLPED eyes were significantly lower compared to s-MLPED eyes (DN-MLPED:4; s-MLPED:12; p = 0.03) (Median follow-up: DN-MLPED = 26 months; s-MLPED = 54 months; p = 0.15). Subretinal hyperreflective-material (SHRM) deposition heralded the onset of multilayering and was seen to progress in all DN-PED eyes and 1/4 eyes of s-MLPED. To conclude, MLPED is a unique form of cicatrizing fibrovascular-PED which can evolve denovo too. Long-standing disease with intermittent or low-grade activity can potentially explain this unique phenomenon. With fewer anti-VEGF therapy, the de-novo MLPED eyes show more visual stability as compared to s-MLPED eyes.

Intraretinal Cysts in Macular Hole: A Structure-Function Correlation Based on En Face Imaging.

PURPOSE: To characterize retinal micromorphic changes on en face optical coherence tomography (OCT) and to determine their role in pathogenesis and visual outcomes in macular hole (MH) surgery. PATIENTS AND METHODS: This is a retrospective, interventional, consecutive case series of 28 eyes undergoing successful MH surgery. Pre- and post-operative en face OCT were manually segmented, and the correlation between parameters such as MH basal diameter and minimal inlet area, area of cyst in inner plexiform layer (IPL) and outer plexiform layer (OPL), percentage of cyst in IPL and OPL, and amount of ellipsoid zone (EZ) defect and external limiting membrane (ELM) defect was performed. Their relationship with visual acuity (VA) outcomes (Group 1: ≥20/60; 14 eyes; Group 2: <20/60; 14 eyes) was also evaluated. RESULTS: A significant positive correlation was noted between the cyst area in OPL and IPL (r=0.768; p<0.001), which in turn were positively correlated with the basal diameter of the MH in all eyes. The cyst area was significantly more in IPL as compared to OPL in all eyes (p=0.049) and in group 2 (p=0.03) but not in group 1 (p=0.62). As compared to group 2, eyes in group 1 had significantly better pre- and post-operative VA, and significantly smaller basal diameter, minimal inlet area, area of cyst in IPL and OPL, and amount of defect in the ELM (postoperative) and EZ (pre- and post-operative), respectively. CONCLUSION: An increase in the basal diameter of the MH is associated with a simultaneous congruous enlargement of the area of cyst in IPL and OPL. Based on these imaging findings, we propose that the possible rationale for the origin of these intraretinal cysts could be a breakdown in the physiological retinal pigment epithelium (RPE) pump due to the anatomical separation of the neurosensory retina from the underlying RPE, ie, "RPE contact loss" theory.

Vitreoretinal Society of India practice pattern survey 2020: Medical retina.

Purpose: The aim of this study was to present the outcomes of the Vitreo-retinal Society of India (VRSI) Practice Pattern Survey 2020 in medical retina. Methods: An online survey of members of VRSI was conducted in April 2020 regarding their practice-patterns on varied medical and surgical retina topics concerning imaging and management approach. The results were evaluated by two independent experts in this field and compared with the evidence and other practice patterns in the world. Results: A total of 107 VRSI members participated in the online survey. Responses were obtained on management of wide-ranging chorioretinal disorders such as Central Serous Chorioretinopathy (CSCR), Polypoidal Choroidal Vasculopathy (PCV), Neovascular age related macular degeneration (n-AMD), Retinal Vein Occlusions (RVO), and Diabetic Retinopathy (DR). Participants were also surveyed regarding their attitudes and perceptions about anti-VEGF practice patterns and role of imaging in their current practice. Each of the survey question responses were then compared to contemporary literature, including evidence-based guidelines, randomized controlled trials (RCTs), real-world evidence and analogous international surveys. Comprehensive analysis related to this has been put forward in the article. Conclusion: This survey represents the contemporary practice patterns amongst vitreoretinal specialists in India. The survey results are vital for fellow practitioners to understand the 'standard of care' practice in medical retina. This will guide them to devise the best possible individualized treatment strategy for most favorable clinical outcomes.

Vitreoretinal Society of India practice pattern survey 2020: Surgical retina.

Purpose: To present the outcomes of the Vitreo-retinal Society of India (VRSI) Practice Pattern Survey 2020 in surgical retina. Methods: An online survey of members of VRSI was conducted in April 2020 regarding their practice patterns on varied medical and surgical retina topics concerning imaging and management approach. The results were evaluated by two independent experts in this field and compared with the evidence and other practice patterns in the world. Results: A total of 107 VRSI members participated in the online survey. Responses were obtained on management of wide-ranging surgical retina topics such as diabetic retinopathy, retinal detachments, Macular Hole, and Epiretinal membranes. Participants were also surveyed regarding their attitudes and perceptions about microscopes with the heads-up display system. Each of the survey question responses were then compared to contemporary literature, including evidence-based guidelines, randomized controlled trials, real-world evidence, and analogous international surveys. Comprehensive analysis related to this has been put forward in the article. Conclusion: This survey represents the contemporary practice patterns among vitreoretinal specialists in India. The survey results are vital for fellow practitioners to understand the "standard of care" practice in surgical retina. This will guide them to devise the best possible individualized treatment strategy for most favorable clinical outcomes.

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases.

INTRODUCTION: To assess the safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab® (Intas Pharmaceuticals, Ahmedabad, India) in chorioretinal disorders under real-world conditions. METHODS: This was a multicenter, retrospective chart review which included patients from 15 centers receiving intravitreal Razumab (IVRz) injections from 2016 to 2020. Patient demographics, ocular examination data, and detailed safety information regarding serious adverse events (SAE) or serious adverse drug reactions (sADR), and non-serious AEs (nsAE) or non-serious ADRs (nsADR) occurring within 1 month of IVRz injections were compiled. RESULTS: A total of 6404 eyes of 6404 patients received 9406 IVRz injections [mean (± SD) = 1.49 (± 0.63)] during 4.25 years. Adverse events were reported after 1978 injections (21.03%): 64.16% nsAE, 32.96% nsADR, 2.37% sADR, and 0.51% SAE. The most frequent adverse events were subconjunctival hemorrhage (8.2% of total injections), transient blurring of vision (6.5% of total injections), and mild ocular pain (5.27% of total injections). Serious ocular (31 cases with retinal pigment epithelial tears [0.33%], two cases of non-infectious vitritis [0.02%], and one case of endophthalmitis [0.01%]) and systemic (seven patients with non-fatal myocardial infarction [0.12%] and six patients with non-fatal cerebrovascular accident [0.09%]) adverse events were infrequent. CONCLUSION: The study reports the largest pooled safety data on IVRz use in a real-world scenario. The results did not raise any new ocular or systemic safety concerns for the biosimilar agent, with the incidence and spectrum of adverse reactions similar to those reported with other anti-vascular endothelial growth factor (anti-VEGF) drugs. The real-world evidence suggests that IVRz is a safe anti-VEGF agent in the management of chorioretinal disorders.

Changing trends in the use of anti-vascular endothelial growth factor (anti-VEGF) biosimilars: Insights from the Vitreoretinal Society of India Biosimilars of Anti-VEGF Survey.

Purpose: The aim of this study was to present the outcomes of the 2018 and 2020 Vitreo-retinal Society of India (VRSI) biosimilars of anti-vascular endothelial growth factor (VEGF) (VIBE) surveys. Methods: An online survey of members of VRSI was conducted in July 2018 and January 2020 regarding their practice-patterns on anti-VEGF biosimilars pertaining to safety, efficacy, pricing, and need for enhanced clinical trials before regulatory approval. Results: In 2018, 112 VRSI members participated, whereas in 2020, 98 society members participated. In both surveys, majority of respondents were aware of biosimilars (96%, 2018 vs. 100%, 2020; P = 0.9) and felt that approval of biosimilar drugs should be made more stringent with larger clinical trials (89%, 2018 vs. 91%, 2020; P = 0.93). An increase in use of ranibizumab-biosimilar (41%, 2018 to 56%, 2020; P = 0.2) and a simultaneous significant decline in use of bevacizumab-biosimilar (9%, 2018 to 2%, 2020; P = 0.04) was noted from 2018 to 2020. From 2018 to 2020, the proportion of respondents satisfied with safety (61% to 68%; P = 0.59) and efficacy (65% to 81%; P = 0.32) of ranibizumab-biosimilar increased. However, during the same period, we noted in reduction in satisfaction levels with safety of bevacizumab-biosimilar (30% to 25%; P = 0.54), whereas satisfaction with its efficacy was stable (29% vs 30%; P = 0.99). A substantial proportion of retina specialists considered that current cost of ranibizumab-biosimilar ($130) was sufficiently low for it to be used as a substitute for Avastin (37%, 2018 and 40%, 2020; P = 0.82). Conclusion: The VRSI surveys reveal that Indian vitreoretinal specialists are familiar with anti-VEGF biosimilars. There was a progressive trend favoring ranibizumab-biosimilar over bevacizumab-biosimilar. One-third of the participants deem the current price of ranibizumab-biosimilar as appropriate to replace Avastin. Simultaneously, the need for enhanced pharmacovigilance and larger clinical trials are warranted for regulatory approval of these agents.