Role of Intravitreal Dexamethasone Implant in the Management of Treatment-Naive Diabetic Macular Edema: A Pre-Cataract Surgical Approach for Patients with Systemic Contraindications to Anti-VEGF Therapy.

Purpose: Diabetic macular edema (DME) is a significant cause of vision impairment, posing challenges in its management due to variable responses and patient diversity. While anti-vascular endothelial growth factor (anti-VEGF) agents have revolutionized DME treatment, some patients are not suitable candidates for this therapy. Intravitreal corticosteroid therapy, such as the dexamethasone implant (DEX), has emerged as an alternative. This study aimed to comprehensively investigate the role of intravitreal DEX in treatment-naive DME patients with systemic contraindications to anti-VEGF therapy, administered one month before cataract surgery. Patients and Methods: A single-center retrospective study included 20 eyes with controlled diabetes, visually significant cataracts, untreated DME, and systemic contraindications for anti-VEGF therapy. Patients underwent DEX treatment followed by cataract surgery after one month. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were assessed at multiple time points. Results: BCVA significantly improved on days 30, 90, and 180 post-DEX (P<0.00001). CMT showed a significant decrease at day 30 (P<0.00001), which was sustained through days 90 and 180 (P<0.00001). Recurrent DME was observed in 25% of eyes on day 90. IOP increased significantly at days 30 (P<0.00001) and 90 (P=0.0006), returning to baseline by day 180. However, only two eyes needed topical anti-glaucoma treatment. No other ocular or systemic adverse events were noted. Conclusion: Intravitreal DEX administered one month before cataract surgery offers a promising treatment strategy for treatment-naive DME patients with systemic contraindications to anti-VEGF therapy. The study's findings provide insights into improving visual acuity and reducing macular thickness, along with manageable IOP changes. This personalized approach is a valuable addition to DME management, especially for complex medical cases, warranting further research and consideration for clinical practice.

Efficacy of an Indian Bevacizumab BIOSimilar (BEVATAS) for Type 1 and Aggressive Posterior Retinopathy of Prematurity (BIOS-ROP Study).

Purpose: To evaluate the role of an Indian bevacizumab biosimilar (Bevatas®), for the management of type 1 retinopathy of prematurity (ROP) and aggressive posterior ROP (APROP) over 24-weeks. Patients and Methods: A retrospective, single-center, interventional study of 144 eyes of type 1 (100 eyes) and APROP (44 eyes). All eyes received a single dose of 0.625mg Bevatas injection, and were advised additional laser therapy for suboptimal response. Results: The study population had a mean gestational age of 28.94 (±2.32) weeks, an average birth weight of 1.2 (±0.34) kg, and modest male predominance (52.05%). Complete regression of ROP was seen in 65.97% of 144 eyes after 24 weeks of bevacizumab monotherapy, and in 97.22% of eyes (140 eyes) after adding laser photocoagulation. The remaining four eyes (all had APROP) developed Stage 4 ROP and needed vitreous surgery. After monotherapy with bevacizumab biosimilar, type 1 ROP eyes had significantly higher rate of complete ROP regression than APROP eyes (87% vs 18.18%; P<0.00001). All eyes with type 1 ROP, and 90.91% of eyes with APROP, regressed after receiving additional laser therapy. The study population experienced no ocular or systemic adverse effects. Conclusion: The BIOS-ROP study demonstrates that intravitreal bevacizumab biosimilar monotherapy offers significant benefit for type 1 ROP, but not APROP. Low-cost biosimilars can help sustain healthcare systems in lower-middle income countries (LMICs) with escalating healthcare expenditures. They can also improve healthcare equity by making vision-saving therapies like bevacizumab more affordable and accessible.

Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2 years: the REBA extension study.

BACKGROUND: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting. METHODS: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24 months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24 months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications. RESULTS: The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24. CONCLUSION: Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted.

Impact of COVID-19 Pandemic on Retinopathy of Prematurity Services in the Indian Public Healthcare System.

Purpose: To analyze the impact of the COVID-19 pandemic on the retinopathy of prematurity (ROP) services at Special Newborn Care Units (SNCUs), which provide care for sick neonates in the Indian public healthcare system. Methods: A retrospective chart analysis of 508 babies screened for ROP at two SNCUs in West Bengal (India). We compared the data from the lockdown period (April, 2020-June, 2020; study arm) with the same period of the preceding year, 2019 (control arm). Results: Out of the 508 babies, 187 were screened during the lockdown and 328 during 2019. The odds of developing ROP were 2.08 times (95% CI:1.25-3.48; P=0.002) higher during the lockdown period (35/187 babies; 18.72%) as compared to the previous year (34/328 babies; 10.37%). Also, the risk of sight-threatening ROP (ST-ROP) increased significantly during the lockdown (12/35 ROP babies; 34.29%) compared to the previous year (4/34 ROP babies; 11.76%) (odds ratio: 3.9; 95% CI:1.1-13.7; P=0.015). Notably, all babies with ROP during the lockdown presented more than 30 days after birth, compared to none in the previous year. All babies requiring laser therapy recovered completely in both groups. Conclusion: An increased odds of developing ROP, including ST-ROP, was observed during the COVID-19 pandemic. Delayed ROP screening, which was noted in all study eyes, can have a detrimental effect on long-term visual prognosis. The findings of our research call for modifying the present healthy policy framework to make it more adaptable to disruptions in healthcare services, given the cyclical nature of the worldwide COVID-19 pandemic.

Response of extra-large pigment epithelial detachment to intravitreal brolucizumab injection.

Purpose: To determine the role of intravitreal injection (IVI) of brolucizumab for extra-large pigment epithelial detachment (PED) secondary to macular neovascularization (MNV). Observations: A prospective, non-randomized, uncontrolled case series of three eyes of three patients with extra-large PED (maximum height >350 µm) due to untreated MNV was undertaken at a single center. All three eyes showed significant improvement in the PED height by week 4, with complete resolution by week 8 in two of the three. The third patient who received the second dose is scheduled for a follow-up. Simultaneous notable visual improvement was also observed in all of the eyes. Furthermore, there were no ocular or systemic safety concerns in any of the cases. Conclusions and Importance: Our real-world case series indicates that intravitreal brolucizumab is efficacious and safe for the management of extra-large PEDs in treatment-naïve MNV eyes. To better understand brolucizumab's mechanism of action, particularly at the sub-RPE and choroidal levels, and the underlying functional principle for the PED response, more study of the drug's pharmacotherapeutics is warranted.

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.

Management of Submacular Hemorrhage Using Intravitreal Brolucizumab with Pneumatic Displacement: A Case Series.

The management of submacular hemorrhage (SMH) necessitates rapid clearing of the bleed for optimal visual outcomes. We present a series of 3 cases with large fresh SMH (≤7 days) secondary to MNV that were treated with intravitreal injection (IVI) of brolucizumab along with SF6 gas injection. A face-down position was recommended for 5 days after the injection, with follow-up visits at regular intervals. All eyes demonstrated notable improvement in visual acuity with complete resolution of SMH lasting up to 6 months. There were no ocular or systemic side effects. Thus, IVI brolucizumab with SF6 gas injection is efficacious and safe for the management of large SMH secondary to MNV.

Intravitreal Brolucizumab for Choroidal Neovascularization Associated to Angioid Streaks.

A 44-year-old-female with angioid streak- (AS-) associated choroidal-neovascularization (CNV) was treated with one dose of intravitreal brolucizumab (IB). At one-month, the patient's visual acuity (VA) improved from 20/120 to 20/40 with a dry macula on spectral-domain optical-coherence tomography (SD-OCT). After observation, the VA improved further to 20/32 with absence of any fluid on the SD-OCT at three months. No ocular or systemic adverse events were noted. In conclusion, intravitreal brolucizumab (IB) is an efficacious and safe therapeutic option for the management of CNV secondary to AS. Further prospective studies with a larger sample size, varied therapeutic regimens, and longer follow-up period are needed to corroborate our findings.

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.

Contralateral Effect following Intravitreal Brolucizumab Injection in Diabetic Macular Edema.

The authors describe a novel case of a 48-year-old male with bilateral diabetic macular edema (DME) who underwent intravitreal injection (IVI) of brolucizumab in the left eye. At four weeks, the patient demonstrated a bilateral response by way of improvement in the best-corrected visual acuity (BCVA) and reduction in the central macular thickness (CMT) in both eyes. Further studies on the ocular and systemic assays of the brolucizumab molecule are warranted to evaluate its systemic escape and to better understand the pharmacokinetics behind the bilateral effect.

Screening, isolation and optimization of anti-white spot syndrome virus drug derived from marine plants.

OBJECTIVE: To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various marine floral ecosystems and to evaluate the efficacy of the same in host-pathogen interaction model. METHODS: Thirty species of marine plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. By means of chemical processes, the purified anti-WSSV plant isolate, MP07X was derived. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. RESULTS: Nine plant isolates exhibited significant survivability in host. The drug MP07X thus formulated showing 85% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of MP07X required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 1 000 mg/kg body weight/day survived at the rate of 85%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. CONCLUSIONS: The drug MP07X derived from Rhizophora mucronata is a potent anti-WSSV drug.

Screening, isolation and optimization of anti-white spot syndrome virus drug derived from terrestrial plants.

OBJECTIVE: To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various terrestrial plants and to evaluate the efficacy of the same in host-pathogen interaction model. METHODS: Thirty plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. The best anti-WSSV plant isolate, TP22C was isolated and further analyzed. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. RESULTS: Seven plant isolates exhibited significant survivability in host. The drug TP22C thus formulated showed 86% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of TP22C required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 750 mg/kg body weight/day survived at the rate of 86%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. CONCLUSIONS: The drug TP22C derived from Momordica charantia is a potent anti-white spot syndrome virus drug.

Serous macular detachment as a predictor of resolution of macular edema with intravitreal triamcinolone injection.

BACKGROUND AND OBJECTIVE: To evaluate serous macular detachment as a predictor for response of macular edema to intravitreal triamcinolone acetonide. PATIENTS AND METHODS: Sixteen eyes (16 patients) with macular edema and serous macular detachment secondary to diabetic retinopathy (n = 11) or branch vein occlusion (n = 5) were prospectively enrolled. After intravitreal triamcinolone acetonide injection (4 mg/0.1 mL), they were reevaluated at 1 week and 1 and 3 months. The main outcome measure was change in central macular thickness. RESULTS: The mean baseline central macular thickness was 651.13 +/- 245.96 microm. One month after intravitreal triamcinolone acetonide injection, central macular thickness decreased to 255.38 +/- 80.64 microm (P < .0001). After 3 months, central macular thickness increased marginally to 329.69 +/- 161.98 microm, still significantly less than baseline (P < .0001). There was a significant correlation between the height of serous macular detachment and reduction in central macular thickness at 1 (r = .827) and 3 (r = .835) months (P< .0001). CONCLUSION: When serous macular detachment coexists with vascular or microvascular macular edema, it responds to intravitreal triamcinolone acetonide in direct proportion to the height of the serous macular detachment. However, the response begins to fade by 3 months.

Chronic retinal pigment epithelial detachments with unusual clinical, angiographic, and tomographic presentations.

The authors report two cases of central serous chorioretinopathy of long duration where retinal pigment epithelial detachment presented with unusual clinical features and led to misdiagnosis of a cystic mass lesion in one patient. Fluorescein angiography showed atypical fluorescence patterns, which did not help to diagnose or explain the clinical appearance. Optical coherence tomography confirmed the diagnosis and explained the anatomic basis of the anomalous clinical and angiographic presentation by highlighting the atrophic changes in the retinal pigment epithelial lining of the pigment epithelial detachment in both cases.

Vitrectomy for epimacular membrane secondary to adult-onset Coats' disease.

The authors describe the management of an epimacular membrane secondary to adult-onset Coats' disease. A 26-year-old man presented with decreased vision (20/120) in the right eye for 4 months. Fundus examination revealed features suggestive of Coats' disease, with a thick epimacular membrane. Optical coherence tomography revealed underlying macular thickening. The patient underwent vitrectomy with removal of the epimacular membrane and internal limiting membrane; peripheral telangiectasia were simultaneously photocoagulated. Postoperatively, his visual acuity improved to 20/20, which remained stable for 12 months. Vitrectomy yields an excellent anatomical and functional outcome in epimacular membrane due to adult-onset Coats' disease, if performed before macular exudation leads to subretinal fibrosis.

A live cysticercosis in anterior chamber leading to glaucoma secondary to pupilary block.

A 28-year-old woman presented with pain and redness in her left eye. On examination, a free-floating cyst of size 4 mm with prominent scolex was observed in the anterior chamber. Scolex was occasionally moving in and out of its bag. To prevent the cyst migrating to the posterior chamber, pilocarpine eye drops were instilled. After 2 hours, the patient developed total pupilary block with iris bombe. The intraocular tension was 48 mm Hg. The diagnosis of cysticercosis leading to glaucoma secondary to pupilary block was made. The cyst was removed surgically by viscoexpression. The histopathology proved to be a cysticercosis.