Comparison of different agents and doses of anti-vascular endothelial growth factors (aflibercept, bevacizumab, conbercept, ranibizumab) versus laser for retinopathy of prematurity: A network meta-analysis.

Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. - 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2-2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events.

Toxicity to intravitreal melphalan in a patient with retinoblastoma.

Objective: Description of melphalan's toxicity in retinoblastoma treatment. Methods: Clinical case report. Results: We presented a case of unilateral retinoblastoma with vitreous seeding at diagnosis, in which the use of intravitreal melphalan produced many adverse reactions. Conclusions: Vitreous seedings have been one of the most important challenges in retinoblastoma treatment. Intravitreal melphalan has achieved the regression of vitreous seedings in a large percentage of cases. It is a safe treatment; however, it can produce toxicity, even with the standard dose of 20-30 µg, which has been poorly documented. Exhaustive follow-up of patients is recommended for an early diagnosis of possible adverse effects. Abbreviations: OS = left eye, RI = magnetic resonance imaging, OCT = optical coherence tomography.

Prophylactic effect of brimonidine to minimize the incidence of subconjunctival hemorrhage in the early postoperative period after 23G pars plana vitrectomy.

BACKGROUND: Several studies have investigated and demonstrated the prophylactic effect of brimonidine drops in preventing subconjunctival hemorrhage in some microincisional ophthalmic surgeries, such as intravitreal injections or cataract surgery. However, there are no previous studies investigating this prophylactic effect after 23G microincisional vitreoretinal surgery. AIM: The aim of the current study was to determine whether subconjunctival hemorrhage after 23G pars plana vitrectomy (PPV) could be prevented with the use of prophylactic topical brimonidine. METHODS: This was a phase III, prospective, interventional, randomized, controlled single-center clinical trial with a follow-up of 2 weeks. A total of 77 eyes (mean age: 68.4 ±â€„10.7 years) undergoing 23G PPV were included and randomized into two groups: group 1 including 41 patients receiving prophylactic preoperative treatment with brimonidine, and group 2 (control group) including 36 patients not receiving this prophylactic treatment. Differences in terms of number of conjunctival quadrants affected with subconjunctival hemorrhage were evaluated in each of the follow-up visits. RESULTS: The presence of subconjunctival hemorrhage was similar in both groups the first days after surgery (p > 0.05). At the last visit (10-14 days after surgery), this condition was significantly more frequent in control group where there was a significant difference, being more frequent in the control group (7.3% vs 28.6%, p = 0.022). The number of conjunctival quadrants affected was also similar in both groups, except for the last visit in which most of the patients treated with brimonidine (92.7%) showed no bleeding compared to 71.4% in control group. No effect on the efficacy of brimonidine treatment of the presence of blood hypertension, diabetes, and antiplatelet or anticoagulant treatment was observed. CONCLUSION: Brimonidine seems to be a useful option to decrease subconjunctival hemorrhage after microincisional vitreoretinal surgery or improve its resolution during the first postoperative week. This finding should be mainly due to the vasoconstrictor effect of brimonidine. TRIAL REGISTRATION: EudraCT, 2012-002895-15 (registered 19 December 2012); https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-002895-15.

INTRAVITREAL RANIBIZUMAB INJECTION AND RETINAL LASER PHOTOCOAGULATION TREATMENT FOR ADULT-ONSET COATS DISEASE.

PURPOSE: To describe the evolution of a case of adult-onset Coats disease and the results of treatment with intravitreal ranibizumab and laser photocoagulation. METHODS: Observational case report. CASE REPORT: A 17-year-old girl presented with vision loss in her right eye (20/50) showing aneurysmatic and abnormal telangiectatic vessels associated with profuse lipid exudation and serous retinal detachment within the temporal posterior pole. The diagnosis of Coats disease was established and therapy with intravitreal injections of ranibizumab and photocoagulation was initiated achieving control of the exudative manifestations leading to restoration of visual acuity (20/20). CONCLUSION: Treatment with antiangiogenic agents before laser photocoagulation may be useful for treatment of adult-onset Coats disease.

PROGRESSION OF ABCA4-RELATED RETINOPATHY: Prognostic value of demographic, functional, genetic, and imaging parameters.

PURPOSE: To investigate the prognostic value of demographic, functional, genetic, and imaging parameters on retinal pigment epithelium atrophy progression secondary to ABCA4-related retinopathy. METHODS: Patients with retinal pigment epithelium atrophy secondary to ABCA4-related retinopathy were examined longitudinally with fundus autofluorescence imaging. Lesion area, perimeter, circularity, caliper diameters, and focality of areas with definitely decreased autofluorescence were determined. A model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study. RESULTS: Sixty-eight eyes of 37 patients (age range, 14-78 years) with a follow-up time of 10 to 100 months were included. The mean annual progression of retinal pigment epithelium atrophy was 0.89 mm. The number of atrophic areas, the retina-wide functional impairment, and the age-of-onset category constituted significant predictors for future retinal pigment epithelium atrophy growth, explaining 25.7% of the variability. By extension of a simulated study length and/or specific patient preselection based on these baseline characteristics, the required sample size could significantly be reduced. CONCLUSION: Trial design based on specific shape-descriptive factors and patients' baseline characteristics and the adaption of the trial duration may provide potential benefits in required cohort size and absolute number of visits.

Prevalence, incidence and future projection of diabetic eye disease in Europe: a systematic review and meta-analysis.

To examine the prevalence and incidence of diabetic eye disease (DED) among individuals with diabetes in Europe, a systematic review to identify all published European prevalence and incidence studies of DED in individuals with diabetes managed in primary health care was performed according to the MOOSE and PRISMA guidelines. The databases Medline, Embase and Web of Science were searched to 2 September 2017. Meta-analyses and meta-regressions were performed. The pooled prevalence estimates were applied to diabetes prevalence rates provided by the International Diabetes Foundation atlas and Eurostat population data, and extrapolated to the year 2050. Data of 35 prevalence and four incidence studies were meta-analyzed. Any diabetic retinopathy (DR) and diabetic macular edema (DME) were prevalent in 25.7% (95% CI 22.8-28.8%) and 3.7% (95% CI 2.2-6.2%), respectively. In meta-regression, the prevalence of DR in persons with type 1 diabetes was significantly higher compared to persons with type 2 diabetes (54.4% vs. 25.0%). The pooled mean annual incidence of any DR and DME in in persons with type 2 diabetes was 4.6% (95% CI 2.3-8.8%) and 0.4% (95% CI 0.5-1.4%), respectively. We estimated that persons with diabetes affected by any DED in Europe will increase from 6.4 million today to 8.6 million in 2050, of whom 30% require close monitoring and/or treatment. DED is estimated to be present in more than a quarter of persons with type 2 diabetes and half of persons with type 1 diabetes underlining the importance of regular monitoring. Future health services need to be planned accordingly.

Ocular loiasis affecting a child and its assessment by Anterior Segment Optical Coherence Tomography.

A 9-year-old girl from Equatorial Guinea presented to the emergency department complaining of foreign body sensation in her right eye. A thin and large, translucent, slowly moving, coiled worm was observed underneath the conjunctiva. Anterior segment optical coherence tomography revealed hyperreflective small areas surrounded by larger hyporeflective areas into the subconjunctival space. Loa loa microfilaria was evidenced on blood test. Surgical extraction of the subconjunctival worm was intended on slit lamp and under sedation in the operating room, but it was unsuccessful due to poor cooperation and rapid migration of the larva into the sub-Tenon's space. The patient received two cycles of oral albendazole and one cycle of diethylcarbamazine before achieving complete microfilaria seroconversion. Abbreviations: AS-OCT = Anterior Segment Optical Coherence Tomography, PCR = Polymerase Chain Reaction, DEC = diethylcarbamazine.

Prognostic Tomographic Classification of Myopic Choroidal Neovascularization.

BACKGROUND AND OBJECTIVES: To investigate the prognostic value of the development of a hyperreflective envelopment of the neovascular tissue in myopic choroidal neovascularization (mCNV) after the first intravitreal ranibizumab injection and to establish a tomographic classification of mCNV depending on this healing process. PATIENTS AND METHODS: Twenty-five eyes of 25 patients with mCNV were retrospectively studied. Patients were classified into type A (presence of a hyperreflective coating of the neovascular tissue 1 month after first intravitreal ranibizumab) and type B (absence of or partial coating). Visual acuity (VA) and number of injections were recorded. Differences between both types were assessed at 6 and 12 months of follow-up. RESULTS: Fifteen patients (60%) were classified as type A and 10 as type B (40%). Type A showed better VA than type B. VA improvement was only significant for type A. No differences in the number of injections were observed; however, a trend to a larger amount in type B was observed. CONCLUSIONS: The proposed classification may have prognostic value, with type A mCNV showing better visual outcomes. Further studies are needed to confirm these findings. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:775-779.].

Optical Coherence Tomography Characterization of Macular Changes Secondary to Arteriovenous Fistula.

Arteriovenous fistulas (AVFs) are abnormal shunts between the arterial and venous vascular systems. These usually produce ocular pain, increased intraocular pressure (IOP), and diplopia. Less frequently, they may cause retinal changes with visual impairment. Our purpose is to illustrate different retinal manifestations of AVF. We report the multimodal imaging study of three cases with retinal changes due to AVF, showing neurosensory retinal detachment, macular oedema, and macular ischemia. In conclusion, AVF may appear with different ophthalmic alterations. While usually increased IOP and diplopia are our main concerns, retinal study is mandatory, since a myriad of morphologic abnormalities might be present.

Diagnosis and Treatment Options for Achromatopsia: A Review of the Literature.

Achromatopsia is a complex inherited retinal disease that affects the cone cell function. It is usually an autosomal-recessive disease and is characterized by pendular nystagmus, poor visual acuity, lack of color vision, and marked photophobia. CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6 gene mutations have been identified as associated with this disease. New diagnostic and therapeutic tools are being studied. Optical coherence tomography and fundus autofluorescence are important imaging techniques that provide significant information about the progression of the disease. The genetic approach for these patients is a current important issue and gene therapy is an ongoing therapeutic option already being studied in clinical trials. The purpose of this review was to survey the current knowledge on diagnosis and treatment options in achromatopsia. [J Pediatr Ophthalmol Strabismus. 2018;55(2):85-92.].

Spontaneous closure of traumatic macular hole in a pediatric patient.

We present the case of a 14-year-old boy with ocular trauma and the complete eye-tracking OCT imaging follow-up of the development and later spontaneous closure of a secondary macular hole.

Sarcoid-like reaction in a patient with uveitis and underlying cancer.

PURPOSE: Sarcoidosis is a granulomatous disease of unknown etiology. Occasionally, triggering causes are identified, such as neoplasms, and they are termed sarcoid-like reactions, which may appear in any sarcoidotic target tissue. Choroidal metastases appear as part of widespread metastatic disease or as the first suggestion of neoplastic disease. They can also be a part of the differential diagnosis of a spectrum of inflammatory eye diseases. We present a case in which a lung carcinoma, pulmonary and eye sarcoid-like reactions, and choroidal metastasis take place in the same patient. CASE REPORT: A 60-year-old male with a past history of pulmonary sarcoidosis and associated anterior uveitis was diagnosed with a lung carcinoma with no regional lymph nodes extension, so that the resection surgery was performed without additional systemic treatment. At the same time, he complained of visual acuity loss and pain in his right eye. An intense ocular inflammatory reaction and a choroidal mass compatible with metastasis were identified. A vitrectomy with an accompanied histological exam of the lesion was deemed inconclusive. Ocular symptoms progressively worsened showing mass growth, and as a result, an enucleation was performed and the histological study subsequently revealed metastasis from his lung carcinoma. CONCLUSION: Sarcoid-like reactions may be due to incipient malignancies. Any diagnosis of sarcoidosis requires ruling out other diseases that can produce secondary sarcoid-like reactions. In addition, any choroidal mass suggestive of metastasis requires exclusion of metastatic disease even in the absence of clinical signs indicating tumor extension.

Macular retinal and choroidal thickness in unilateral relentless placoid chorioretinitis analyzed by swept-source optical coherence tomography.

BACKGROUND: The purpose of this study is to evaluate the retinal and choroidal thickness of the macular region in patients with unilateral relentless placoid chorioretinitis (RPC) and macular involvement. Patients diagnosed with RPC affecting only one eye underwent a comprehensive ophthalmologic examination including best-corrected visual acuity (BCVA), axial length (AL) measurement, slit-lamp examination, and color fundus and autofluorescence photography. The macular region was scanned by swept-source optical coherence tomography in the 1,050-nm wavelength. Automated segmentations of the retina and the choroid were used to obtain the corresponding thickness values. RESULTS: A total number of three patients (two men and one woman; age range 17 to 62 years) were included. Eyes with clinically evident RPC had a mean AL of 24.62 ± 0.11 mm, whereas in the clinically healthy fellow eyes, the mean AL was 24.65 ± 0.03 (p = 0.70). The mean BCVA was 0.93 ± 0.16 in eyes with RPC, and 1.0 in all the fellow eyes (p = 0.70). Slit-lamp examination did not reveal any sign of vitreous inflammation in any cases. The mean macular retinal thickness was 288.10 ± 10.22 µm in eyes with RPC, and 300.30 ± 7.17 µm in the healthy fellow eyes (p = 0.20). The mean central choroidal thickness was 260.70 ± 140.60 µm in eyes with RPC, and 262.30 ± 123.10 µm in the fellow eyes (p = 0.99). The mean macular choroidal thickness was 248.60 ± 128.40 and 255.10 ± 123.60 µm, respectively (p = 0.99). CONCLUSIONS: The pathogenesis of RPC remains unknown. No changes in the retinal and choroidal thickness were observed in the macular area of eyes diagnosed with RPC with macular involvement compared with the asymptomatic healthy fellow eyes. Further prospective studies are warranted in order to investigate the role of the choroid in cases of RPC.

Massive bilateral serous retinal detachment in a case of hypertensive chorioretinopathy.

INTRODUCTION: Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. CASE REPORT: A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. DISCUSSION: In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes.

Update on intravitreal anti-tumor necrosis factor alpha therapies for ocular disorders.

Tumor necrosis factor alpha (TNF-?) is an important pro-inflammatory cytokine associated with a variety of ocular diseases. The currently available TNF-? inhibitors are etanercept, infliximab, adalimumab, golimumab, and certolizumab. Experimental and clinical studies on the intravitreal use of these agents have been reported with etanercept, infliximab, and adalimumab: etanercept has shown limited efficacy in scarce reports; infliximab has been associated with local safety concerns but appears to benefit certain cases; adalimumab has shown no efficacy in cases of age-related macular degeneration (AMD) or diabetic macular edema (DME), but the combination with bevacizumab may be effective in refractory cases of macular diseases. Further preclinical and clinical studies are warranted in order to be able to obtain a more robust conclusion on the use of intravitreal TNF-? inhibitors.