Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To assess the noninferiority of biosimilar aflibercept (P041, CinnaGen) to the originator aflibercept (AFL, Regeneron) in terms of efficacy, safety, and immunogenicity. DESIGN: This was a phase Ш, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio. SUBJECTS: Patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the 2 groups of P041 and AFL. METHODS: Patients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week 48. MAIN OUTCOME MEASURES: The primary outcome was the noninferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity and retinal thickness, safety evaluation, and immunogenicity during the study. RESULTS: In total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in the P041 group compared with 94.52% in the AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined noninferiority margin of 10% (difference, -0.0008; 95% CI, -0.074 to 0.074; P = 0.98). Secondary outcomes indicated similar results in both arms (all P > 0.05). Safety measured outcomes and immunogenicity were similar between the 2 study groups. CONCLUSIONS: Biosimilar aflibercept was noninferior to AFL in eyes with neovascular age-related macular degeneration. Other efficacy and safety findings also indicated the similarity of 2 products. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Automated machine learning-based classification of proliferative and non-proliferative diabetic retinopathy using optical coherence tomography angiography vascular density maps.

PURPOSE: The study aims to classify the eyes with proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR) based on the optical coherence tomography angiography (OCTA) vascular density maps using a supervised machine learning algorithm. METHODS: OCTA vascular density maps (at superficial capillary plexus (SCP), deep capillary plexus (DCP), and total retina (R) levels) of 148 eyes from 78 patients with diabetic retinopathy (45 PDR and 103 NPDR) was used to classify the images to NPDR and PDR groups based on a supervised machine learning algorithm known as the support vector machine (SVM) classifier optimized by a genetic evolutionary algorithm. RESULTS: The implemented algorithm in three different models reached up to 85% accuracy in classifying PDR and NPDR in all three levels of vascular density maps. The deep retinal layer vascular density map demonstrated the best performance with a 90% accuracy in discriminating between PDR and NPDR. CONCLUSIONS: The current study on a limited number of patients with diabetic retinopathy demonstrated that a supervised machine learning-based method known as SVM can be used to differentiate PDR and NPDR patients using OCTA vascular density maps.

Pars plana vitrectomy combined with phacoemulsification versus pars plana vitrectomy only for treatment of phakic rhegmatogenous retinal detachment: a systematic review and meta-analysis.

PURPOSE: To compare the visual, refractive, and anatomical outcomes and incidence of complications between combined pars plana vitrectomy and phacoemulsification (phacovitrectomy) versus pars plana vitrectomy (PPV-only) in phakic eyes with rhegmatogenous retinal detachment (RRD). METHODS: Two independent reviewers searched MEDLINE, Cochrane Central, and Web of Science to identify relevant articles. Prospective or retrospective studies comparing PPV-only and phacovitrectomy for RRD were included. Recruited studies provided information about at least anatomical success or refractive outcomes. Meta-analysis was performed for single surgery success rate, final best-corrected visual acuity (BCVA), postoperative complications, mean predicted refractive error, and mean absolute predicted refractive error. RESULTS: Seven studies (788 eyes) were selected, including two clinical trials and five retrospective comparative case series. The single surgery success rate was similar in PPV-only and phacovitrectomy groups (risk ratio [RR] = 1.02; 95% confidence interval [CI] 0.95-1.10; P = 0.57). Mean final BCVA was significantly better in the PPV-only group than the phacovitrectomy group (MD = 0.06; 95% CI 0.00-0.12; P = 0.04). The risk of epiretinal membrane formation was significantly higher in eyes that underwent phacovitrectomy than PPV-only (RR = 2.85; 0.95% CI 1.5-5.41; P = 0.001). Phacovitrectomy group showed a more myopic final mean predicted refractive error than PPV-only group (MD = -0.31; 95% CI -0.55--0.07; P = 0.01). CONCLUSION: There was no significant difference between the two groups regarding the anatomical outcome. Slightly better visual and refractive results were observed in the PPV-only group. However, the results should be interpreted with caution as the majority of included studies were low-quality retrospective studies.

Evaluation of the additive effect of interferon α 2b with monthly intravitreal injection of bevacizumab in refractory diabetic macular edema.

BACKGROUND: To evaluate the additive effect of topical or sub-tenon injection of interferon (IFN)-α 2b in the treatment of refractory diabetic macular edema. METHODS: In this prospective study patients with center-involved DME who were unresponsive to 3 monthly consecutive IVB injections were recruited. Patients were divided into three groups: group1, received IFN- α 2b topical drop at a dose of 1mIU/ml four times a day for 3 months. Group 2, received a single sub-tenon injection of 1mIU/ml IFN- α 2b at the enrollment. Group 3 received artificial tears four times a day for 3 months (control group). All groups received three consecutive monthly IVB injections and were evaluated monthly up to 1 month following the last IVB injection. RESULTS: In this study, 59 eyes of 35 patients with refractory DME were assessed. The final follow-up showed that although CMT decreased in all groups, only patients in Group 2 had statistically significant lower CMT compared to their baseline values (change in CMT: - 117 ± 213 µm; p-value = 0.025). Comparison of CMT changes between three groups showed no statistically significant difference, although it was higher in group 2 (change in CMT: - 117 ± 213 µm (Group2) vs. - 49 ± 173 (Group 1) vs. - 36 ± 86 (Group 3); p-value = 0.085). Considering eyes with baseline CMT > 400 µm, sub-tenon injection of IFN α2b led to a significant reduction of CMT at the first month and final follow-up visit (CMT change: - 166 ± 210, - 145 ± 231 µm; p-value = 0.018 and 0.035, respectively). In this subgroup, eyes in Group 2 had lower CMT at the first month following treatment in comparison with the control group (CMT: 444 ± 123 µm vs. 544 ± 96 µm, p-value = 0.042). Alterations of CDVA were not statistically significant among groups, although patients in Group 1 had a significant improvement in vision at second and last follow up (CDVA change: - 0.23 ± 0.39, - 0.20 ± 0.43 logMAR; p-value = 0.030 and 0.010, respectively). CONCLUSIONS: In short term, Sub-tenon injection of IFN might have an additive anatomical effect in eyes with refractory DME. Validation of this observation requires further prospective controlled studies.

Optical Coherence Tomography Angiography Findings in Malignant Hypertensive Retinopathy.

Purpose: To report the findings of fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) in a patient with malignant hypertensive retinopathy. Case Report: A 41year-old male was referred to our clinic with sudden visual loss in both of his eyes after an acute rise of blood pressure (200/150 mmHg). Optic disc swelling, flame shape hemorrhages especially around the optic disc, arterial narrowing, vessel tortuosity, cotton wool spots, hard exudate deposition, and multiple deep orange spots (Elschnig spots) were visible in both eyes. In the OCTA, disruption in the normal tapering patterns of the superficial and deep capillary plexuses was observed. Elschnig spots were observed as hypointense spots in the choriocapillaris slab. Leakage of the optic nerve head was seen in the FA. Conclusion: When compared with the FA, the OCTA can illustrate the ischemic areas and the Elschnig spots with greater detail.

Flat irregular pigment epithelial detachment over time and outcome of different treatment regimens.

To present long-term visual and structural outcome of treatment in two forms of flat irregular pigment epithelial detachment (FIPED): avascular (aFIPED) and vascularized (vFIPED) in eyes within pachychoroid spectrum. Prospective interventional case series. FIPED were classified into two subgroups; aFIPED and vFIPED based on OCTA. aFIPED underwent PDT, and vFIPED underwent either PDT, IVB, or combination of PDT&IVB. Vision, subretinal or intraretinal fluid, and choroidal biomarkers such as choroidal thickness, area, choroidal vascular index (CVI), and PED area were measured at baseline and last follow-up. Fifteen eyes with aFIPED were followed for a mean of 14.7 ± 10.8 months. Their vision improved, (0.44 ± 0.37-0.33 ± 0.40 LogMAR, p = 0.009) with significant reduction of fluid, choroidal area, thickness, PED area and increase in CVI. Twenty eyes with vFIPED were followed for a mean of 16.5 ± 8.2 months. The same pattern of choroidal alterations without visual improvement was observed in eyes underwent PDT alone. Combination therapy resulted in improvement of vision (0.38 ± 0.10-0.23 ± 0.17 LogMAR, p = 0.006) with reduction of choroidal area and thickness, with an increase in CVI. IVB alone could not change vision or choroidal structure. Single session PDT may lead to sustained visual improvement and structural change in eyes with aFIPED. Combination of PDT and IVB may be a better choice in eyes with vFIPED.

Management of primary choroidal lymphoma presenting as extensive serous retinal detachment and salmon patch of bulbar conjunctiva: a case report.

BACKGROUND: We describe the outcome of ultra-low-dose radiotherapy plus intravitreal methotrexate and rituximab injections for a patient with primary choroidal lymphoma who presented with nodular conjunctival salmon patches and extensive serous retinal detachment. CASE PRESENTATION: A 34-year-old Iranian man presented with a nodular patch of bulbar conjunctiva in the right eye, and 1+ vitritis. A nearly complete shallow serous retinal detachment, retinal folds, and multifocal yellow choroidal infiltrates were seen during a fundus examination of the right eye. Enhanced depth imaging optical coherence tomography revealed macular retinal folds and an uneven, undulating, "seasick" appearance of the choroidal surface with choriocapillaris compression, intraretinal and subretinal fluid, and clusters of optically dense material at the outer retinal level. An incisional biopsy of the conjunctival lesion confirmed the diagnosis of primary choroidal lymphoma with epibulbar involvement. The patient was treated with ultra-low-dose "boom-boom" radiation (4 Gy delivered in two fractions over two consecutive days) as well as intravitreal methotrexate and rituximab injections. After a year, the lesions had completely disappeared, with no adverse effects or recurrence. CONCLUSION: Ultra-low-dose (boom-boom) radiotherapy combined with intravitreal chemotherapy and/or immunotherapy may be an effective treatment for primary choroidal lymphoma with anterior epibulbar extension and diffuse subretinal fluid with favorable response and minimal side effects.

Alterations in choroidal vascular parameters following panretinal photocoagulation using enhanced-depth imaging optical coherence tomography in diabetic retinopathy.

PURPOSE: To investigate the alteration of choroid in patients with very severe non-proliferative diabetic retinopathy (NPDR) or early proliferative diabetic retinopathy (PDR) following panretinal photocoagulation (PRP). METHODS: Thirty-nine eyes of 21 patients with very severe non-proliferative diabetic retinopathy (NPDR) (19 eyes) and early proliferative diabetic retinopathy (PDR) (20 eyes) were recruited. Enhanced-depth imaging optical coherence tomography at baseline, 1, and 6 months after PRP was employed to measure choroidal parameters including total choroidal area (TCA) and choroidal vascular index (CVI). RESULTS: In eyes with very severe NPDR, subfoveal TCA decreased non-significantly at month 1, which increased significantly at month 6 (539 ± 131µm2, 502 ± 134µm2, and 598 ± 168µm2 at baseline and months 1 and 6, respectively; P = 0.003). Subfoveal CVI increased at month 1 and then decreased at month 6 (68.25 ± 3.05, 69.74 ± 3.62, and 67.84 ± 1.77 at baseline and months 1 and 6, respectively; P < 0.001). A reverse pattern occurred in eyes with early PDR, a non-significant increase in TCA at month 1 followed by a decrease at month 6 (497 ± 95µm2, 514 ± 133µm2, and 425 ± 95µm2 at baseline and months 1 and 6, respectively; P = 0.011). CVI decreased at month 1 and remained relatively stable at month 6 (69.34 ± 3.11, 68.33 ± 3.41, and 68.50 ± 5.04 at baseline, and months 1 and 6, respectively; P = 0.023). Alteration of choroidal thickness was not statistically significant in both groups. CONCLUSION: Eyes with very severe NPDR and early PDR exhibit a reverse pattern regarding choroidal indices after PRP.

Erratum: Optical Coherence Tomography Angiography Findings in Malignant Hypertensive Retinopathy.

[This corrects the article DOI: 10.18502/jovr.v17i3.11583.].

A Novel Approach for Development of Intraocular Biodegradable Ranibizumab Implant: A Solution for Stability of Protein Activity.

Purpose: Ranibizumab is a monoclonal antibody fragment, targeting all isoforms of vascular endothelial growth factor A (VEGF-A), a protein involved in angiogenesis. It is used to treat age-related macular degeneration (AMD), retinal vein occlusion (RVO), and diabetic macular edema (DME), which are associated with blindness worldwide. However, proper treatment can decrease the loss of vision in about 90% of patients. Because of poor drug uptake in topical therapy and several adverse side effects of systemic irregularities and intravitreal injections, sustained-release drug delivery systems are more suitable for treatment. However, there are many challenges in the development of these systems due to the loss of protein activities. Methods: After drug complexation by the ion pairing method and preparation of a polymeric implant, containing the drug, the characteristics of the complexes were examined by Fourier-transform infrared spectroscopy and circular dichroism spectroscopy. The stability of antibody activity and biocompatibility of the released drug from the implant were assessed by bioassays and MTT assay, respectively. Finally, the release kinetics were investigated. Results: The bioassays showed the higher activity of the drug complex, compared to the free form, besides good biocompatibility in vitro. Also, the release data confirmed sustained and controlled release characteristics for the prepared implant. Conclusion: In this study, for the first time, we proposed a method for developing a sustained-release intraocular implant, consisting of ranibizumab by the heating method. This method allows for the industrial production of ranibizumab by extrusion and eliminates the complications related to reservoir systems.

Sickle Cell Trait Presenting as Unilateral Proliferative Retinopathy and Macular Thinning in a Pregnant Woman.

BACKGROUND: To report a case of a pregnant woman with sickle cell trait (SCT) who presented with unilateral proliferative sickle cell retinopathy. Case Presentation. A 26-year-old otherwise healthy pregnant woman presented with the complaint of visual loss in her left eye. The funduscopic examination showed vitreous hemorrhage, sea fan neovascularization, and pale optic disc. Optical coherence tomography revealed macular inner retinal layer thinning and foveal splaying (saucerization of the foveal pit). The investigations, including hemoglobin electrophoresis, verified the diagnosis of sickle cell trait. Blood pressure, fasting blood glucose tests, and tuberculin skin tests were normal. We treated the patient by peripheral retinal photocoagulation over the area of nonperfusion. CONCLUSION: Even though the sickle cell trait is generally considered as a milder form of sickle cell disease without severe retinal manifestations, pregnancy should be considered as a trigger that can induce proliferative changes and foveal splaying in this group of patients.

Choroidal features in flat irregular pigment epithelial detachment associated with Chronic central serous chorioretinopathy: Avascular versus vascularized.

PURPOSE: To investigate the differences in the choroidal biomarkers between two forms of flat irregular pigment epithelial detachment (FIPED): avascular (aFIPED) and vascularized (vFIPED) in eyes with chronic central serous chorioretinopathy (CSC). MATERIALS AND METHODS: Enhanced depth imaging optical coherence tomography (EDI-OCT) was done in eyes with FIPED correlated to chronic CSC, fellow eyes, and also in healthy eyes from gender- and age-matched subjects. Eyes with FIPED were classified into two subgroups based on optical coherence tomography angiography (OCTA) findings: vFIPED and aFIPED. Different choroidal biomarkers such as subfoveal choroidal thickness (SFCT), total choroidal area (TCA), and choroidal vascular index (CVI) were compared between the groups. RESULTS: Forty-four eyes from 42 patients with chronic CSC and FIPED along with 40 eyes from 20 healthy subjects were included. OCTA identified vascularization in 14 eyes in the FIPED group (31.8%). Mean SFCT was higher in the FIPED group compared to two other groups (p = 0.005). In comparison to patients with aFIPED, patients with vFIPED had lower SFCT (p = 0.003) and higher CVI (p = 0.020) based on multivariate analysis. CONCLUSIONS: It seems that measurement of CVI along with SFCT may help to differentiate aFIPED from vFIPED in patients with CSC. Further longitudinal studies would be required to confirm the clinical significance of these findings.

Photopigment Bleaching Phenomenon on Fluorescein Angiography in a Patient with Impending Central Retinal Vein Occlusion.

PURPOSE: To present the second case of photopigment bleaching phenomenon in fluorescein angiography (FA) and the first case of this phenomenon due to impending central retinal vein occlusion (CRVO). CASE REPORT: A 32-year-old healthy female noticed blurred vision in her right eye one day before presentation. Despite the 20/20 visual acuity at presentation, mild increased retinal vascular tortuosity and unilateral photopigment bleaching phenomenon in FA was observed in the right eye. Three weeks later, she developed a complete CRVO with visual acuity reduction to 20/40 that responded well to the intravitreal injection of aflibercept. CONCLUSION: Impending CRVO can cause unilateral photopigment bleaching phenomenon in FA that may be due to retinal ischemia.

Intraocular Injection of StivantⓇ (A Biosimilar to Bevacizumab): A Case Series.

PURPOSE: To report the results of intravitreal injection of a bevacizumab biosimilar called StivantⓇ. METHODS: This prospective interventional case series was conducted on eyes with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), and diabetic macular edema (DME). StivantⓇ was injected in three consecutive months and changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at baseline and monthly up to one month after the third injection. RESULTS: Three hundred and eighty-five eyes with DME (234 eyes, 61%), nAMD (87 eyes, 22%), and macular edema secondary to RVO (64 eyes, 17%) were enrolled. The mean ± standard deviation age of the patients was 61.7 ± 7.20 years. The mean BCVA and CMT changed from 0.63 ± 0.3 to 0.51 ± 0.3 LogMAR (P = 0.12 ) and from 420.4 ± 47.3µm at baseline to 316.7 ± 50.6 µm (P < 0.001) in the DME group; from 0.79 ± 0.3 to 0.68 ± 0.3 LogMAR (P = 0.19) and from 376.1 ± 31.7 µm to 303 ± 31.3 µm (P = 0.019) in the nAMD group; and from 0.81 ± 0.4 to 0.63 ± 0.4 LogMAR (P = 0.05) and from 424.21 ± 18 µm to 303.4 ± 18.8 µm (P < 0.001) in the RVO group, respectively. CONCLUSION: Our limited experience showed that the intravitreal injection of StivantⓇ was well tolerated. Although the results of this case series showed relative improvement in CMT one month after the last injection of StivantⓇ, BCVA improvement was statistically significant only in the RVO group. This would be essential to design a randomized clinical trial to evaluate the non-inferiority of StivantⓇ in comparison to bevacizumab.

Ocular complications following intravitreal bevacizumab injection for retinopathy of prematurity and assessment of risk factors.

PURPOSE: Laser ablation of the avascular peripheral retina has been the standard method of ROP treatment. Intravitreal anti-VEGF is useful in the management of ROP patients, especially for aggressive posterior ROP. However, ocular and systemic complication after intravitreal bevacizumab was the main concern. This study aimed to investigate the treatment-related ocular and systemic complications of intravitreal bevacizumab (IVB) in patients with retinopathy of prematurity (ROP). METHOD: This retrospective study included neonates receiving intravitreal injections of bevacizumab (IVB) (0.625 mg) to treat ROP. Medical records of the patients were evaluated about the ocular complications after receiving IVB from 2012 to 2019. Treatment-related complications (vitreous hemorrhage, glaucoma, cataract, hyphema, corneal abrasion/opacity, and endophthalmitis), and disease-progression signs including retinal fold or stage 4 or 5 detachment were documented. Any reports of systemic events after injections were also recorded. RESULT: Mean gestational age and birth weight of 441 patients receiving IVB for type-1 ROP were 28 ± 2 (22-34 weeks) and 1121 ± 312 (550-2700 g), respectively. The median follow-up after treatment in all patients and patients with complications was 289.43 ± 257 days (5-1899 days) and 385.89 ± 311.59 (196-1192) days, respectively. Out of 865 eyes, 20 eyes (2.31%, 95% Clopper-Pearson Confidence Interval: 1.14-3.54%) have been affected by ocular complications. The rates of different complications included progression of retinopathy in 17 eyes (1.96%), cataracts in 2 eyes (0.23%), and vitreous hemorrhage in one eye (0.11%). No cases of endophthalmitis, thromboembolic events, or death occurred in this study. We evaluated the prevalence ratio (PR) on the multiple risk factors to determine the prediction of the complications. The existence of neovascularization of iris has the highest susceptibility to predict the complication (PR = 5.091, P-value 0.014) following by the presence of retinopathy in zone 1 of the infant's retina (PR = 4.386, P-value = 0.010). CONCLUSION: The incidence rate of complications related to Intravitreal bevacizumab injection was low, which was compatible with previous studies. Bevacizumab injection seems well tolerated in most cases of ROP. Iris neovascularization and the presence of retinopathy in zone 1 were associated with a higher occurrence of complications than the absence of these risk factors.

Effect of panretinal photocoagulation on macular vasculature using optical coherence tomography angiography.

BACKGROUND: To evaluate the changes of macular vascular density in the superficial capillary (SCP) and the deep capillary plexus (DCP), foveal avascular area (FAZ), choroidal flow, and macular thickness after pan-retinal photocoagulation (PRP). METHODS: In this prospective interventional non-comparative case series, patients with very severe nonproliferative (NPDR) and early proliferative diabetic retinopathy (PDR) and no significant macular edema who were candidates for pan-retinal photocoagulation underwent measurement of corrected distance visual acuity (CDVA), optical coherence tomography (OCT), Optical coherence tomography angiography (OCTA) at the baseline, 1, and 6 months following completion of PRP treatment. RESULTS: Thirty-nine eyes from 21 patients with diabetes were enrolled. Superficial and deep capillary plexus densities in the foveal and parafoveal area didn't change significantly 1 and 6 months post-PRP (p > 0.1 in all of them). The FAZ area constricted 6 months following PRP (p = 0.075). Based on the calculated circularity index, the FAZ became significantly more circular after 6 months of follow-up (p = 0.047). Although the choroidal flow area increased after PRP this increase wasn't statically significant neither at 1 month nor at 6 months post-PRP (p = 0.31 and 0.23, respectively). CONCLUSION: Although OCTA parameters were not significantly affected by PRP at both short-term (1 month) and long-term (6 months) follow-ups, the FAZ area became significantly circular after PRP may be due to redistribution of blood flow in hypoperfused foveal capillary plexus.

Safety of Intravitreal Injection of Stivant, a Biosimilar to Bevacizumab, in Rabbit Eyes.

PURPOSE: To evaluate the safety of intravitreal injection of Stivant, a biosimilar to bevacizumab, in rabbits using electrophysiological and histological analysis. METHODS: Both eyes of 41 New Zealand albino rabbits were injected with 0.1 mL (2.5 mg) of Stivant. The rabbits were scheduled to be sacrificed 1, 2, 7, 14, and 28 days after injection for histopathological evaluations. Clinical examinations and electroretinography (ERG) were performed at baseline and just before sacrificing the rabbits. Fourteen separate rabbits received a reference drug (Avastin) and were considered as the control group. Furthermore, three other rabbits received the same volume of saline (saline control group). Rabbits of both control groups were sacrificed four weeks after injection. ERG was performed 1, 2, 7, 14, and 28 days after injections. RESULTS: No significant difference was observed in a- and b-wave amplitudes and latency after intravitreal Stivant injection between baseline and different time points. Moreover, there was no statistically significant difference in wave amplitudes and latency between the Stivant and control groups. The histology of rabbit eyes of the Stivant and control groups after intravitreal injections was not distinguishable. CONCLUSION: The biosimilar Stivant, up to a dose of 2.5 mg, did not appear to be toxic to the retina in albino rabbits. These results suggest that this drug could be a safe and inexpensive alternative to intravitreal bevacizumab. The efficacy of these injections was not investigated in this study and needs to be evaluated in future studies.

Safety of Intravitreal Injection of Biosimilar of Aflibercept in Rabbit Eyes.

PURPOSE: To assess the safety of biosimilar intravitreal aflibercept (CinnaGen Co., Iran) compared to the reference product (Eylea®; Bayer Schweiz AG, Zurich, Switzerland) in rabbit eyes through functional and histologic studies. METHODS: Forty New Zealand albino rabbits were recruited to the study and were divided into four groups to be sacrificed at 48 hours, one, two, and four weeks after injections. In each group, five rabbits received 0.05 mL (2 mg) biosimilar aflibercept in the right eye and 0.05 mL saline in the left eye as the control, and in a similar manner, the remaining five rabbits received the reference drug in the right eye and saline in the left eye. All the rabbits underwent comprehensive ophthalmic examination and electroretinography (ERG) tests at baseline and also just before enucleation at the specific predefined time points. The enucleated eyes were prepared for retinal toxicity histological examination. RESULTS: No retinal toxicity was observed based on histologic and ERG findings in all groups. Choroidal congestion was revealed after 1 week in an eye that was injected with biosimilar aflibercept, although the similar finding was detected in the contralateral eye which received saline. Also, one subject which received the reference drug showed chronic vitritis and lymphoplasmocytic reaction of the optic disc at week 4. The remaining subjects showed no histologic changes. CONCLUSION: The 2 mg intravitreal injection of biosimilar aflibercept (CinnaGen Co., Iran) was found to be nontoxic in rabbit eyes in the short-term period. Further studies are required to warrant the efficacy and safety profile of the drug in human subjects.

Optical coherence tomography angiography in best vitelliform macular dystrophy.

PURPOSE: To report best vitelliform macular dystrophy (BVMD) with an intriguing pattern of vascular flow on optical coherence tomography angiography (OCTA). METHODS: Four eyes of two patients with BVMD were evaluated. Complete ophthalmic examination including best corrected visual acuity (BCVA), spectral domain optical coherence tomography (SD-OCT), and OCTA were performed. Diagnosis was confirmed by electroretinography (ERG) and electrooculography (EOG) testing. RESULTS: All eyes had the electrophysiologic confirmation of the BVMD. The first patient was 35 years old with BCVA of 20/20 and pseudohypopyon stage macular lesion in right eye (RE) and BCVA of 20/32 and vitelliruptive stage macular lesion in the left eye (LE). The second patient was 18 years old with BCVA of 20/25 and macular lesion in vitelliform stage in the RE and BCVA of 20/60 and choroidal neovascularization (CNV) in the LE. In all eyes, a distinct foveal avascular zone (FAZ) was not detectable in OCTA, with a bridging vessel in the FAZ. A dense subretinal capillary network compatible with CNV in the LE of second patient was observed. CONCLUSION: In our cases, we found bridging vessel in the FAZ, and it may be due to the effects of bestrophin on the calcium content and vascular endothelial growth factor (VEGF) secretion of the retinal pigment epithelium (RPE) cells.