Aflibercept vs. dexamethasone implant for recalcitrant diabetic macular edema in pseudophakic eyes - 1-year outcomes from a quazi-randomized study in India.

PURPOSE: To assess the safety and efficacy of intravitreal Aflibercept (IVA) versus dexamethasone (DEX) implant for treating recalcitrant diabetic macular edema (DME) in pseudophakic eyes at 1-year follow-up. DESIGN: Retrospective comparative case series. PARTICIPANTS: Data of all patients diagnosed with DME between January 2019 and December 2021, who underwent 4-monthly doses of intravitreal ranibizumab but had persistent DME [central macular thickness (CMT) within 10% of baseline value] were extracted from a computerized database. Of these, only pseudophakic eyes that underwent either IVA or DEX implant and had at least 1-year follow-up were included for analysis. METHODS: DEX implant was preferred before December 2020 and IVA after this time point. In the IVA group, patients were followed up every month while DEX were followed at least every 3 months. Reinjections were considered when vision dropped by at least 1 Snellen's line or CMT increased by at least 10% from the previous visit in both groups. MAIN OUTCOME MEASURES: Comparison of change in vision and CMT at 1-year follow-up in DEX versus IVA groups. RESULTS: Eighty-four eyes of 84 patients aged 54.4 + 4.4 years were included, 39 (46%) received DEX and 45 (54%) received IVA. Groups were comparable for baseline vision and CMT. Vision improved equally in both groups from 0.83 + 0.15 logMAR to 0.52 + 0.10 logMAR at 3 months (P < 0.01) and then stabilized till 1 year. However, eyes in the IVA group were 6.5 times more likely (Odds ratio = 6.45, 95% CI = 1.3 - 31.9) to achieve >3-line improvement in vision. The CMT reduction was also comparable between groups (-169 + 51 in DEX vs. -174 + 49 in IVA, P = 0.67). More eyes in the IVA group required >3 injections (91% vs. 69% in DEX, P = 0.01). The IOP was significantly higher at 6 and 9 months in the DEX group and 5 eyes (13%) required IOP lowering medications. CONCLUSION: In pseudophakic eyes with recalcitrant DME not responding to ranibizumab, switching to IVA or DEX implant results in equal visual improvement and CMT reduction. Though >3-line improvement occurs more frequently with IVA, this comes at the expense of a greater number of injections and follow-up visits.

Short-Term Treatment Outcomes of Brolucizumab in Patients with Neovascular Age-Related Macular Degeneration: A Multicentre Indian Real-World Evidence Study.

Objective: To evaluate the short-term effectiveness and safety outcomes following brolucizumab treatment in patients with neovascular age-related macular degeneration (nAMD) as a part of real-world clinical practice in India. Methods: This was a retrospective, observational, multicentre study including patients (≥50 years old) diagnosed with nAMD. Anonymized data of the patients receiving the first dose of brolucizumab intravitreal injection (IVI) who were either treatment-naïve or previously treated with a single or a combination of other anti-VEGF IVIs were included. The present study reported the change in retinal fluid levels from baseline to month 3, best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of injections received. The adverse events in the three months after brolucizumab treatment initiation were also monitored. Results: The study included 63 patients (65 eyes) from four study centres across India (mean age: 69.1 ± 9.7 years). A total of 82 brolucizumab injections were administered during the 3 months of study duration, with 52/65 (80.0%) eyes receiving only 1 injection. Resolution of IRF, SRF, and PED was observed in 76.9%, 64.6%, and 67.7% of eyes, respectively. Further, a significant reduction in CRT was observed (baseline: 403.5 ± 118.7 µm; month 3: 308.3 ± 73.8 µm; p < 0.001), and BCVA also improved notably from 0.7 ± 0.5 logMAR at baseline to 0.5 ± 0.4 logMAR at month 3 (p < 0.001). Adverse events (AEs) were reported in 3 eyes from 3 patients; retinal pigment epithelial rip (1) and subretinal hemorrhage (2) after the first injection of brolucizumab, however, none discontinued the treatment. Conclusion: The study reports on the short-term effectiveness and tolerability of brolucizumab therapy in the management of nAMD in both treatment-naïve and switch eyes. Brolucizumab was observed to have a favourable benefit-risk profile, and study results were within the known safety profile, with no instances of intraocular inflammation.

Incidence, clinical features, risk factors, and outcomes of Intraocular inflammation following Brolucizumab in Indian eyes - A multicentric study.

Purpose: To report the incidence, clinical features, potential risk factors, and outcomes of intraocular inflammation (IOI) following brolucizumab in Indian eyes. Methods: All consecutive patients diagnosed with brolucizumab-induced IOI from 10 centers in eastern India between October 2020 and April 2022 were included. Results: Of 758 injections given during the study period across centers, 13 IOI events (1.7%) were recorded attributable to brolucizumab. The IOI occurred after the first dose in two eyes (15%) (median 45 days after brolucizumab), second dose in six eyes (46%) (median = 8.5 days), and third dose (39%) in the remaining five eyes (median 7 days). Reinjections of brolucizumab were administered at a median interval of 6 weeks (interquartile range = 4-10 weeks) in the 11 eyes, where IOI occurred after the second or third dose. Eyes that experienced IOI after the third dose had received a significantly greater number of previous antivascular endothelial growth factor injections (median = 8) compared to those who developed it after the first or second dose (median = 4) (P = 0.001). Anterior chamber cells were seen in almost all eyes (n = 11, 85%), while peripheral retinal hemorrhages were seen in two eyes, and one eye showed branch artery occlusion. Two-thirds of patients (n = 8, 62%) recovered with a combination of topical and oral steroids, while remaining recovered with topical steroids alone. Irreversible visual loss was not seen in any eye, and median vision recovered to pre-IOI levels by 3 months' time point. Conclusion: Brolucizumab-induced IOI was relatively rare, occurring in 1.7% of eyes, was more common after the second or third injection, especially in those who required frequent reinjections every 6 weeks, and occurred earlier with increasing number of previous brolucizumab injections. Continued surveillance is necessary even after repeated doses of brolucizumab.

Real-world outcomes and complications of different surgical approaches for significant submacular haemorrhages.

Purpose: To evaluate the outcomes and complications after different surgical management of cases with significant sumacular hemorrhage (SMH) of size more than 4 disc diameter (DD). Methods: It was a retrospective interventional study. All consecutive 103 cases of significant SMHs were treated by vitrectomy and divided into three groups. In Group A (<4 weeks, confined to the macula or extending inferiorly, n = 62), vitrectomy, subretinal cocktail of tissue plasminogen activator (tPA), antivascular endothelial growth factor, and air with SF6 gas; in Group B (4-8 weeks, extending beyond macula, n = 31), subretinal tPA followed by SMH drainage either by retinotomy (Group B-1, n = 17) or by temporal 180-degree retinectomy (Group B-2, n = 14) with silicone oil (SO) tamponade; and in Group C (>8 weeks, extending beyond macula, n = 10), SMH removal with autologous retinal pigment epithelium (RPE)-Choroid patch graft transplantations with SO tamponade were performed. Parameters evaluated were best corrected visual acuity (BCVA), Optos, optical computerized tomography, and ultrasonography as required. Results: Significant visual improvement was seen from mean preoperative to mean postoperative BCVA in Group A (P < 0.001), Group B (P < 0.001), and Group C (P < 0.001). Postoperative complications were recurrent SMH (4.84% vs 12.90% vs 10%), vitreous hemorrhage (6.45%, GroupA), hyphema (4.84% vs 12.90% vs 10%), hypotony (nil vs 3.23% vs 20%), macular hole formation (6.45%, Group A), epiretinal membrane (16.13%, Group B), and retinal detachment (3.23%, Group A and 10%, Group C). Conclusion: Surgical approaches for significant submacular hemorrhage are visually awarding, though certain specific complications may arise.

Biosimilar versus InnovAtor MoLecule of RAnibizumab in Neovascular Age-Related MaCular DEgeneration (The BALANCE Trial): Real-World Evidence.

Purpose: To analyse outcomes of innovator ranibizumab (IRM) (Lucentis) and biosimilar ranibizumab (BRM) (Razumab) in Indian eyes with neovascular age-related macular degeneration (nAMD). Methods: Retrospective observational study in nAMD patients, who were treated with IRM or BRM (3 loading doses followed by pro re nata (PRN). Primary outcome measures were change in best corrected visual acuity (BCVA) and central macular thickness (CMT) along with safety analysis. Secondary outcomes measures were changes in the subretinal fluid (SRF) and intraretinal fluid (IRF). Results: Inclusion criteria were satisfied in 164 eyes (60.74%). A total of 87 eyes were treated with IRM, and 77 eyes received BRM. Baseline BCVA was 0.57±0.27 logMAR in IRM group and 0.61±0.25 in the BRM group. At 3, 6, 9, and 12 months BCVA was 0.27±0.22 (p<0.0001), 0.34±0.23 (p<0.0001), 0.39±0.25 (p<0.0001), and 12 months 0.41±0.23 (p<0.0001) in the IRM group and 0.24±0.16 (p<0.0001), 0.27±0.16 (p<0.0001), 0.34±0.17 (p<0.0001), 0.38±0.18 (p<0.0001) in the BRM group. Baseline CMT was 420.39±54.45 µm in IRM group and 407.82±53.07 µm in BRM group. At 3, 6, 9, and 12 months, CMT decreased to 258.28±20.4 µm (p<0.0001), 268.38±19.5 µm (p<0.0001), 269.51±32.41 µm (p<0.0001), and 278.28±16.56 µm (p<0.0001) in the IRM group and 258.84±17.47 µm (p<0.0001), 265.69±17.29 µm (p<0.0001), 273.64±23.13 µm (p<0.0001), and 283.09±19.66 µm (p<0.0001) in the BRM group. Similar improvements in IRF and SRF levels in the patients were noted in both groups. Required number of doses of IRM and BRM was similar over the 12 month period in both groups. A similar profile of adverse events was noted in both the groups. Conclusion: Intravitreal injection of IRM and BRM show similar efficacy and safety in Indian eyes with nAMD.

Complete manuscript title: role of sub-silicone oil application of triamcinolone acetonide (TA) drops on outcomes after 360° relaxing retinectomy: a pilot study.

PURPOSE: To perform a pilot study to evaluate the role of sub-silicone oil Triamcinolone Acetonide (TA) crystal drops in complex Retinal Detachment (RD) with extreme proliferative vitreoretinopathy (PVR) requiring 360-degree relaxing retinectomy (RR). DESIGN: It was a retrospective pilot study. MATERIALS AND METHODS: It was a retrospective case-control pilot study. TA-assisted 23G or 25G vitrectomy was done in 24 complex RDs with extreme PVR where 360 degree RR had to be performed. Group A (n = 13) included cases where additional TA crystal drops were applied, after settling the detached retina, over the site of RR under silicone oil (SO 5000 CSt) tamponade. In the control arm, group B (n = 11), additional TA crystals were not applied. MAIN OUTCOMES MEASURED: Mean pre- and post-operative BCVA, ultra-widefield fundus photograph by Optos 200Tx, macular OCT and the propensity to remove silicone oil were measured. RESULTS: Mean pre-operative and post-operative BCVA at final follow-up were Log MAR 2.69 ± 0.41 and Log MAR 1.51 ± 0.90 (Mann-Whitney U test, p < 0.05), respectively, in Group A and Log MAR 2.9 and Log MAR 2.37 ± 0.86 (Mann-Whitney U test, p < 0.05), respectively, in group B. Visual improvement in group A was significantly better than group B (Wilcoxon W test, p < 0.025) with significantly less recurrence of RD (Fisher's Exact Test, p = 0.002). Silicone oil removal was done significantly more in group A (Fisher's Exact Test, p = 0.0017). CONCLUSION: Sub-silicone oil crystals application over sites of RR after 360-degree relaxing retinectomy leads to improved postoperative visual recovery as well as improved anatomical outcomes with fewer complications.

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.

Intravitreal Injection of Brolucizumab for Recalcitrant Macular Edema due to Central Retinal Vein Occlusion: A Small Case Series.

This was a single center, prospective uncontrolled nonrandomized case series. Two eyes with recalcitrant ME secondary to CRVO, who have received a minimum of ten intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, underwent IVI brolucizumab (BRZ). Patients underwent best corrected visual acuity (BCVA) testing, ophthalmic examination, and optical coherence tomography at baseline and follow-up visits (weeks 4, 8, 12, and 16). Both patients demonstrated notable improvement in BCVA and reduction of fluid on SD-OCT lasting up to week 12. At week 16, though both the eyes maintained the visual acuity gains, early increase in fluid was noted in both cases, for which second dose of IVI BRZ was given. No ocular or systemic adverse events were noted in these 2 cases.

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 µm at baseline to 289 ± 25 µm (P < 0.001) at the last follow-up period. None of the eyes experienced any intraocular inflammation across 48 injection sessions. Conclusion: Brolucizumab is safe and effective in controlling PCV disease in both treatment-resistant and treatment-naïve eyes.

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.

Comparison of Innovator vs. Biosimilar Ranibizumab in Treating Diabetic Macular Edema: A Multicenter Retrospective Study.

INTRODUCTION: To compare the efficacy of innovator ranibizumab (iRBZ-Accentrix, Novartis, India) vs. biosimilar ranibizumab (bRBZ, Razumab-Intas, India) in eyes with diabetic macular edema (DME) in an Indian population. METHODS: Data of patients with DME who underwent at least three injections of iRBZ or bRBZ and had a minimum of 6 months follow-up were obtained from an electronic database. Choice of injection depended upon the patient. Pro re nata (PRN) protocol from baseline was used with reinjections advised if the central macular thickness (CMT) was at least 300 µm and best corrected visual acuity (BCVA) was 20/40 or worse. Primary outcome measure was comparison of change in BCVA at 6 months between iRBZ and bRBZ. RESULTS: We included 264 eyes in the iRBZ group and 69 eyes in bRBZ group, which were comparable for baseline characteristics. Mean BCVA improved from 0.64 ± 0.39 logMAR to 0.47 ± 0.31 logMAR (p < 0.001) in the iRBZ group and from 0.71 ± 0.42 logMAR to 0.50 ± 0.29 logMAR in the bRBZ group (p < 0.001) at 6 months. There were no differences in BCVA between the two groups (p > 0.05 for all time points). The CMT reduction in the iRBZ group (120 ± 196 µm) was comparable to that in the bRBZ group at 6 months (105 ± 187 µm) (p = 0.69). There was no difference in the mean number of injections taken (3.81 ± 1.2 in iRBZ vs. 3.55 ± 1.2 in bRBZ) (p > 0.05) between groups. Vision at baseline was the only factor associated with vision at last follow-up after adjusting for CMT at baseline, type of injection, and number of injections. CONCLUSIONS: Biosimilar RBZ is similar to innovator RBZ in improving vision and reducing CMT in eyes with DME in the short term.

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 m vs. 246 ± 34m; 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 1/3rd of a line better in the BVZ group (b 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.

A Delphi method based consensus statement for surgical management of proliferative diabetic retinopathy in India.

PURPOSE: To derive consensus statements for surgical management of proliferative diabetic retinopathy (PDR) for vitreoretinal (VR) surgeons. METHODS: Thirteen prolific VR surgeons representing all regions of India were invited to participate in a 42-point questionnaire based on the Delphi methodology describing various surgical scenarios commonly encountered in PDR. Consensus was derived using predefined robust analytics. Scenarios that returned a moderate consensus in round 1 were taken to round 2 as per the Delphi methodology. After considering all inputs, the final consensus criteria were developed. RESULTS: A strong consensus was derived about waiting for 4 weeks before considering vitrectomy. In treatment-naïve eyes with fresh vitreous hemorrhage (VH), the wait time was slightly shorter for extramacular tractional retinal detachment (2-4 weeks) and longer (4-6 weeks) for eyes treated previously with laser or anti-VEGF agents. The expert panel recommended using preoperative anti-VEGF only in eyes with large membranes requiring extensive dissection. For post vitrectomy VH, while a conservative approach was recommended for the first episode of VH, experts recommended immediate vitreous lavage for recurrent episodes of VH. In eyes with iris neovascularization, the panel recommended immediate anti-VEGF injection followed by early vitreous lavage in nonresponsive eyes. A strong consensus was derived for stopping antiplatelet agents before surgery, while there was only a moderate consensus for performing vitrectomy for recalcitrant macular edema unresponsive to anti-VEGF injections in the absence of traction. CONCLUSION: This study provides valuable consensus on managing the different scenarios encountered during surgical management of PDR and should help guide the VR surgeons in clinical decision-making.