Intravitreal Medications for Retinal Vein Occlusion: Systematic Review and Meta-analysis

Purpose: To evaluate the outcomes of different intravitreal injections for the treatment of retinal vein occlusion including central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Methods: PubMed, Cochrane, the metaRegister of ControlledTrials, and ClinicalTrials were searched for intravitreal anti-Vascular Endothelial Growth Factor (VEGF) and steroids with relevant keywords and date limitation of 2009-2018. Meta-analysis was performed on studies that met the defined inclusion criteria. Main outcomes were visual acuity (VA) and central macular thickness (CMT). Results: Out of 681 studies, 36 articles (including 21 reporting CRVO and 15 dealing with BRVO) were selected for systematic review. All five intravitreal drugs including triamcinolone, dexamethasone, ranibizumab, bevacizumab, and aflibercept showed improvement of CMT and VA as compared to placebo or laser treatment. Six randomized controlled trials were selected for meta-analysis in RVO patients. The pooled mean difference of visual improvement between sham and ranibizumab was 12.7 Early Treatment for Diabetic Retinopathy Study (ETDRS) letters (95%CI: 11.00 to 13.2), and the pooled mean difference in CMT reduction was 221 μm (95%CI: 153 to 284); both changes were significantly in favor of ranibizumab. The pooled mean difference of visual improvement between bevacizumab and triamcinolone was 5.3 ETDRS letters in favor of bevacizumab (95%CI: 16 μm to 17.5 μm). Triamcinolone led to 68.1 μm greater CMT reduction than bevacizumab (95%CI: 58 μm to 76 μm). However, none of these differences were statistically significant. Conclusion: Treatment with anti-VEGF agents in RVO is superior to observation. No significant difference was seen between the eyes treated with bevacizumab or triamcinolone based on these results

Renal Function following Fluorescein Angiography in Diabetic Patients with Chronic Kidney Disease

Purpose: To evaluate the effect of fluorescein dye usage on renal function in patients with diabetic retinopathy (DR) and chronic kidney disease (CKD). Methods: Diabetic patients with retinopathy who were candidate for fundus fluorescein angiography (FA) were evaluated for serum creatinine and urea levels within five days prior to performing the FA. Serum creatinine levels of 1.5 mg/dl or more in males and 1.4 mg/dl or more in females were both identified as CKD and were included in the study. An increase of 0.5 mg/dl or 25% in creatinine after FA was considered as contrast-induced acute kidney injury (AKI). Estimated glomerular filtration rate (eGFR) was also calculated for all patients using a CKD-Epi formula. CKD grading was determined based on eGFR values. Results: Forty-two patients agreed to participate, of which 23 (54.8%) were male. Seventeen patients were identified with grade 3a or lower CKD, 12 with grade 3b, 11 with grade 4, and two with grade 5 CKD. Considering all grades of CKD, the mean blood urea before and after angiography was 58.48 ± 26.7 and 57 ± 27.81 mg/dl, respectively (P = 0.475). The mean serum creatinine before and after the test was 1.89 ± 1.04 and 1.87±0.99 mg/dl, respectively (P = 0.993). The mean eGFR before and after the test was 44.024 ± 23.5447 and 43.850 ± 21.8581 mL/min/1.73 m2 (P = 0.875). Conclusion: According to the findings of this study, FA does not seem to further deteriorate kidney function in patients with diabetic associated CKD

Comparison of Three Different Techniques of Inverted Internal Limiting Membrane Flap in Treatment of Large Idiopathic Full-Thickness Macular Hole.

Purpose: To evaluate and compare three different techniques of inverted internal limiting membrane (ILM) flap in the treatment of large idiopathic full-thickness macular hole. Methods: In a comparative interventional case series, 72 eyes from 72 patients with large (\u3e 400 µm) full-thickness macular hole were randomly enrolled into three different groups: group A - hemicircular ILM peel with temporally hinged inverted flap; group B - circular ILM peel with temporally hinged inverted flap; and group C - circular ILM peel with superior inverted flap. Best-corrected visual acuity (BCVA), anatomical closure rate, and ellipsoid zone (EZ) or external limiting membrane (ELM) defects were evaluated preoperatively, at week 1, and months 1, 3 and 6 after surgery. Results: There were 24 eyes in group A, 23 in group B, and 25 in group C. In all three groups, larger diameter macular hole was associated with worse preoperative visual acuity (r=0.625, P\u3c0.001). Mean BCVA improved significantly in all three groups 6 months after surgery (0.91vs 0.55, p\u3c0.001). 6 months after surgery, mean BCVA improved from 0.91 logMAR to 0.52±0.06 in group A, 0.90 to 0.53±0.06 in group B, and 0.91 to 0.55±0.11 in group C. In group A vs. B vs. C, improvement of BCVA was 0.380±0.04 vs. 0.383±0.04 vs. 0.368±0.11 logMAR, with no statistically significant difference between groups (P=0.660). The rate of successful hole closure was 87.5% vs. 91.3% vs. 100%. Although the closure rate was 100% in Group C (circular ILM peel with superiorly hinged inverted flap), this difference was not statistically significant (P=0.115). Conclusion: ILM peel with an inverted flap is a highly effective procedure for the treatment of large, full-thickness macular hole. Different flap techniques have comparable results, indicating that the technique can be chosen based on surgeon preference

Application of ImageJ in Optical Coherence Tomography Angiography (OCT-A): A Literature Review

Background. This study aimed to review the literature on the application of ImageJ in optical coherence tomography angiography (OCT-A) images. Methods. A general search was performed in PubMed, Google Scholar, and Scopus databases. The authors evaluated each of the selected articles in order to assess the implementation of ImageJ in OCT-A images. Results. ImageJ can aid in reducing artifacts, enhancing image quality to increase the accuracy of the process and analysis, processing and analyzing images, generating comparable parameters such as the parameters that assess perfusion of the layers (vessel density (VD), skeletonized density (SD), and vessel length density (VLD)) and the parameters that evaluate the structure of the layers (fractal dimension (FD), vessel density index (VDI), and lacunarity (LAC)), and the foveal avascular zone (FAZ) that are used widely in the retinal and choroidal studies), and establishing diagnostic criteria. It can help to save time when the dataset is huge with numerous plugins and options for image processing and analysis with reliable results. Diverse studies implemented distinct binarization and thresholding techniques, resulting in disparate outcomes and incomparable parameters. Uniformity in methodology is required to acquire comparable data from studies employing diverse processing and analysis techniques that yield varied outcomes. Conclusion. Researchers and professionals might benefit from using ImageJ because of how quickly and correctly it processes and analyzes images. It is highly adaptable and potent software, allowing users to evaluate images in a variety of ways. There exists a diverse range of methodologies for analyzing OCTA images through the utilization of ImageJ. However, it is imperative to establish a standardized strategy to ensure the reliability and consistency of the method for research purposes

Dosimetric Investigation of Six Ru-106 Eye Plaques by EBT3 Radiochromic Films and Monte Carlo Simulation

Background: Ophthalmic brachytherapy using radioactive plaques is an effective technique for the treatment of uveal melanoma. Ru-106 eye plaques are considered as interesting issue due to their steep gradient dose. The pre-planning evaluation of dosimetric parameters is essential for the treatment planning system.Objective: The current study aims at providing dose distributions of six Ru-106 eye plaques (CCA, CCB, CGD, CIB, COB and COD) using radiochromic EBT3 film, Geant4 Monte Carlo toolkit and the treatment planning software (Plaque Simulator).Material and Methods: In this experimental study, an in-house phantom was employed for depth dose measurements with EBT3 films. Also, Geant4.10.5 scoring mesh was implemented to obtain the 2D dose distribution of the plaques. The results were compared with Plaque Simulator software and the manufacturer’s (BEBIG) data. The gamma index criterion (3%/3 mm) was used to evaluate dose distributions obtained by the film measurements and Geant4 simulation.Results: A good agreement was achieved between simulation and experimental results. Gamma index passing rate was 94.2%, 89.3%, 88.2%, 82.2%, 92.2% and 90.1% for CCA, CCB, CGD, CIB, COB and COD plaques, respectively. Absolute dose rate (mGy/min) obtained by EBT3 film at the depth of 2 mm was 79.4 mGy/min, 81.0 mGy/min, 78.6 mGy/min, 62.2 mGy/min, 75.2 mGy/min and 81.2 mGy/min for CCA, CCB, CGD, CIB, COB and COD plaques, respectively.  Conclusion: The measured dose distributions and lateral dose profiles may be utilized in the treatment planning system to cover clinical volumes such as the clinical target volume and the gross tumor volume

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

Massive Uveal Relapse of Retinoblastoma Presumed to Be Choroidal Tumorous Involvement: Case Series

We report the choroidal and ciliary body invasion by retinoblastoma (RB) in a salvaged eye after complete and successful primary treatment. Case 1: A 25-month-old boy was referred due to group B RB lesions based on the International Classification of RB (ICRB; groups A–E) in the right eye (OD). His left eye (OS) was enucleated because of advanced group E RB. After 47 months of uneventful follow-up (F/U), a new lesion recurred and was treated with transpupillary thermotherapy. Four months later, a fast-growing pigmented subretinal mass was detected that was treated by brachytherapy with the apical dose of 80 Gy. Three weeks later, the lesion regressed completely, and no recurrence happened after 6 years of F/U. Case 2: A 4-month-old girl with a deletion in chromosome 13 was referred for bilateral RB. OD was enucleated because of unresponsive RB and anterior segment involvement. In OS, group B lesions had multiple recurrences after systemic chemotherapy. After a while, a single mass appeared in the nasal periphery which was controlled well with brachytherapy. Four months later, AC involvement was controlled with IAC, intravitreal, and intracameral chemotherapy, but posterior synechia and cataract appeared later. One year after the last treatment, UBM showed a ring-shaped ciliary body mass. Her parents refused enucleation again, and she received intravenous chemotherapy. Two years later, magnetic resonance imaging showed orbital and optic canal involvement with a deformed globe. In conclusion, RB recurrence can appear as local choroidal and ciliary body involvement even after a time of complete remission. The role of B-scan and UBM in early diagnosis and successful treatment is valuable

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

Strabismus Management in Retinoblastoma Survivors

PURPOSE: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients. METHODS: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist. RESULTS: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2-39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4-9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor\u27s group was D (n = 11), C (n = 4), B (n = 2) and E (n = 1). Macula was involved by the tumors in 12 (67%) patients. The tumors were managed by intravenous chemotherapy (n = 8, 47%), intra-arterial chemotherapy (n = 7, 41%) and both (n = 3, 17%). After complete treatment, the average time to strabismus surgery was 29.9 ± 20.5 (range, 12-84) months. Except for one, visual acuity was equal or less than 1.0 logMAR (≤ 20/200) in the affected eye. Seven (39%) patients had exotropia, 11(61%) had esotropia (P = 0.346) and vertical deviation was found in 8 (48%) cases. The angle of deviation was 42.0 ± 10.4 (range, 30-60) prism diopter (PD) for esotropic and 35.7 ± 7.9 (range, 25-50) PD for exotropic patients (P = 0.32) that after surgery significantly decreased to 8.5 ± 5.3 PD in esotropic cases and 5.9 ± 6.7 PD in exotropic cases (P \u3c 0.001). The mean follow-up after surgery was 15.2 ± 2.0 (range, 10-24) months, in which, 3 (17%) patients needed a second surgery. CONCLUSION: Strabismus surgery in treated Rb is safe and results of the surgeries are acceptable and close to the general population. There was not associated with tumor recurrence or metastasis

Transient complete visual loss and subsequent cystoid macular edema after intracameral lidocaine injection following uneventful cataract surgery

Purpose: To report a case of transient visual loss following uncomplicated cataract surgery with unpreserved intracameral lidocaine. Methods: A 61-year-old woman with nuclear sclerosis cataract underwent uncomplicated phacoemulsification and in-the-bag intraocular lens (IOL) implantation. Results: After opening the eye patch on the first postoperative day, the patient complained of complete blindness. Her vision was no light perception (NLP) and the Marcus-Gunn was found to be 4+. Eight hours later, the patient's visual acuity improved to count fingers at 1 m. After two days, the vision improved surprisingly to 20/20 without any Marcus-Gunn. After 4 weeks, the vision decreased surprisingly to 20/80 without any Marcus-Gunn. On this day, macular optical coherence tomography (OCT) was performed, and cystoid macular edema was detected. Conclusion: Transient visual loss after intracameral lidocaine has been reported after violation of posterior capsule during cataract surgery, and here, we report a case of transient visual loss despite uncomplicated cataract surgery. Keywords: Intracameral lidocaine, Transient visual loss, Macular edem