Assessment of choriocapillaris/Sattler and Haller layer changes after intravitreal injection in eyes with neovascular age-related macular degeneration: aflibercept vs ranibizumab

Purpose To evaluate the changes in choriocapillaris (CC)/Sattler and Haller layer thicknesses in eyes with neovascular age-related macular degeneration (nAMD) after aflibercept or ranibizumab injections. Study design Retrospective. Methods A total of 70 eyes of 70 patients with treatment-naive exudative nAMD were treated with 3 consecutive injections of aflibercept (IVA) or ranibizumab (IVR). CC/Sattler and Haller layer thicknesses were measured at the nasal and temporal regions 1000 mu m from the center of the fovea by enhanced-depth imaging optical coherence tomography at baseline and after the 3 monthly intravitreal injections. In addition, the hyperfluorescence region (HF) was measured as the largest horizontal diameter of the hyperfluorescence area on the early-middle phase fluorescein angiographic images at baseline and after the 3 loading doses. Results After the 3 consecutive injections, the mean reductions in the nasal/temporal CC/Sattler layer thicknesses in the IVR and IVA groups were - 10.1 +/- 2.3/ - 8.5 +/- 1.8 and - 25.2 +/- 15.2/ - 19.4 +/- 12.8 mu m, respectively. Also, the mean reductions in the nasal/temporal Haller layer thicknesses in the IVR and IVA groups were - 6.5 +/- 3.6/ - 7.2 +/- 7.9 and - 9.5 +/- 8.0/ - 7.0 +/- 6.2 mu m, respectively. The changes in the CC/Sattler layer thicknesses of the IVA group were greater than those of the IVR group (P .05). The mean decrease in the HF size of the IVA group was greater than that of the IVR group (P < .001). Conclusions Aflibercept treatment has a more pronounced effect on the CC/Sattler layer. Such results may indicate that aflibercept treatment influences choroidal neovascularization, possibly by reducing the capillary permeability associated with active neovascularization in the CC layer

Evaluation of the change in retinal thickness after femtosecond laser-assisted laser in situ keratomileusis and photorefractive keratectomy

© 2021 Taylor & Francis Group, LLC.Purpose of the study: To investigate the change in individual retinal layer thickness by spectral-domain optical coherence tomography (SD-OCT) in eyes underwent femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and photorefractive keratectomy (PRK). Methods: In patients who underwent PRK and FS-LASIK, changes in the thickness of all retinal layers in the foveal, parafoveal, and perifoveal regions were evaluated by SD-OCT automated segmentation analysis at pre-operatively and different time points post-operatively. Results: Seventy-one eyes of 71 patients (38 patients in PRK, 33 patients in LASIK) were included. In the pre-operative period, mean spherical equivalent (SE), mean keratometry, axial length, and segmentation values of the retinal layers were similar (P> .05). In the PRK group, the pre-operative measurements of individual retinal layers did not show a statistically significant difference compared to the post-operative measurements on the 1st day, 1st week, and 1st month. In the FS-LASIK group, the mean inner nuclear layer (INL) thickness one day after the surgery was significantly higher than that before surgery in the foveal (21.22 ± 4.66 µm vs 19.03 ± 4.50 µm, P= .013) and parafoveal regions (41.98 ± 3.70 µm vs 40.56 ± 3.49 µm, P= .044). Conclusions: The findings of our study suggest that the increase of INL thickness may be due to temporary structural and circulatory changes of the retina that may occur in the suction phase in the FS-LASIK procedure

Results of surgery for late sequelae of cicatricial retinopathy of prematurity

Purpose: To report anatomical and functional results of vitreoretinal surgery in our case series of late cicatricial retinopathy of prematurity (ROP) patients with subtotal retinal detachment. Methods: This is a retrospective, consecutive case series. Eleven eyes of 10 patients presented with partial tractional retinal detachment secondary to late cicatricial ROP (cicatricial stage 4B) who underwent vitreoretinal surgery were retrospectively reviewed. Anatomical and functional outcomes were evaluated. Results: The mean gestational age at birth was 28.6 (26-32) weeks. The mean age at surgery was 79 (4-213) months. Patients were followed up for 21.7 (6-40) months. Six eyes (55\%) had lens-sparing vitrectomy and five eyes (45\%) had lensectomy + vitrectomy. Anatomical success was achieved in 10 eyes (91\%). Improvement in visual acuity was noted in nine eyes (82\%). Conclusion: Eye grows but fibrotic tissue does not grow with age, and during this period retinal traction may get worse. Relieving these tractions may lead to good anatomical and visual outcomes in selected late cicatricial ROP cases

Apelin-13: A Promising Biomarker for Age-Related Macular Degeneration?

Purpose: To investigate the value of serum apelin-13 levels in patients with age-related macular degeneration (AMD). Methods: Patients with dry-type AMD, patients with treatment-naive neovascular-type AMD, and healthy controls were included in this study. Diagnoses were confirmed on detailed fundus examination, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). Central foveal thickness and subfoveal choroidal thickness were evaluated. Both serum apelin-13 and vascular endothelial growth factor (VEGF) levels were measured by a competitive enzyme-linked immunosorbent assay (ELISA) principle. Results: A total of 84 subjects, i.e., 24 in the dry-type AMD group (group 1), 27 in the neovascular-type AMD group (group 2), and 33 in the control group (group 3) were included in the study. Mean best-corrected visual acuity (BCVA) was 76 +/- 4.5, 48.4 +/- 16.3, and 83.4 +/- 3.09 ETDRS letters in group 1, 2, and 3, respectively. The level of serum VEGF was 44.11 +/- 26.14, 56.53 +/- 53.77, and 61.47 +/- 41.62 pg/mL in groups 1, 2, and 3, respectively (p = 0.553, p = 0.286, and p = 0.896, respectively). The level of serum apelin-13 was 586.47 +/- 167.56, 622.18 +/- 324.52, and 379.31 +/- 171.96 pg/mL in groups 1, 2, and 3, respectively (p = 0.847, p = 0.04, and p <= 0.001, respectively). There was a negative correlation between the level of serum apelin and visual acuity (VA) and choroidal thickness. Conclusion: Serum apelin-13 levels were higher in both dry-type and neovascular-type AMD patients than in controls. Further studies demonstrating the relationship of the level of serum apelin-13 and AMD are needed

Analysis of genotype-phenotype correlation in Walker-Warburg syndrome with a novel <i>CRPPA</i> mutation in different clinical manifestations.

Purpose: Walker-Warburg syndrome (WWS) is a rare autosomal recessive disorder characterized by congenital muscular dystrophy and severe brain and eye malformations. This study aims to analyze genotype-phenotype correlations in WWS with a novel cytidine diphosphate-l-ribitol pyrophosphorylase A (CRPPA) mutation in different clinical manifestations. Case description: We report a girl with a presentation of multiple brain and ocular anomalies. Her ophthalmological evaluation showed a shallow anterior chamber, cortical cataract, iris hypoplasia, persistent hyperplastic primary vitreous in the right eye, punctate cataract, iris hypoplasia, primary congenital glaucoma, and a widespread loss of fundus pigmentation in the left eye. She was hypotonic, and her deep tendon reflexes were absent. Laboratory investigations showed high serum levels of serum creatine kinase. Brain magnetic resonance imaging demonstrated hydrocephalus, agenesis of the corpus callosum, retrocerebellar cyst, cerebellar dysplasia and hypoplasia, cobblestone lissencephaly, and hypoplastic brainstem. Whole exome sequencing revealed a novel homozygous nonsense mutation in the first exon of the CRPPA gene (NM_001101426.4, c.217G>T, p.Glu73Ter). Conclusions: The study findings expand the phenotypic variability of the ocular manifestations in the CRPPA gene-related WWS. Iris hypoplasia can be a part of clinical manifestations of the CRPPA gene-related WWS. The uncovering of the genes associated with ocular features can provide preventative methods, early diagnosis, and improved therapeutic strategies

Genotype-phenotype correlations in ocular manifestations of Marinesco-Sjogren syndrome: Case report and literature review

Purpose: This study aims to present a family with two children with MSS who presented with different ophthalmic features. We also aim to review MSS patients' ocular manifestations to provide a basis for future clinical trials and improve MSS patients' ophthalmologic care. Case description: Both patients presented with global developmental delay, microcephaly, cerebellar ataxia, and myopathy. The older sibling had developed bilateral cataracts at the age of six. Her 2 years younger sister interestingly showed bilateral hyperopic refractive error without cataracts yet. Mendeliome sequencing unraveled a novel homozygous frameshift mutation in the SIL1 gene (SIL1, NM_022464.5, c.1042dupG, p.E348Gfs*4), causing MSS. A systematic literature review revealed that cataracts appear in 96% of MSS cases with a mean onset at 3.2 years. Additional frequent ocular features were strabismus (51.6%) and nystagmus (45.2%). Conclusion: SIL1-related MSS is associated with marked clinical variability. Cataracts can develop later than neuromuscular features and cognitive signs. Since cataract is a relatively late finding, patients may refer to ophthalmologists for other reasons such as refractive errors, strabismus, or nystagmus. Molecular genetic testing for SIL1 is essential to facilitate early diagnosis in patients with suspected MSS

Intravitreal steroids for macular edema in diabetes

BACKGROUND: Diabetic macular edema (DME) is secondary to leakage from diseased retinal capillaries with thickening of central retina, and is an important cause of poor central visual acuity in people with diabetic retinopathy. Intravitreal steroids have been used to reduce retinal thickness and improve vision in people with DME. OBJECTIVES: To assess the effectiveness and safety of intravitreal steroid therapy compared with other treatments for DME. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase on 15 May, 2019. We also searched reference lists, Science Citation Index, conference proceedings, and relevant trial registers. We conducted a top up search on 21 October, 2020. SELECTION CRITERIA: We included randomized controlled trials that evaluated any type of intravitreal steroids as monotherapy against any other intervention (e.g. observation, laser photocoagulation, anti‐vascular endothelial growth factor (antiVEGF) for DME. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and risk of bias and extracted data. Where appropriate, we performed meta‐analyses. MAIN RESULTS: We included 10 trials (4348 participants, 4505 eyes). These trials compared intravitreal steroid therapies versus other treatments, including intravitreal antiVEGF therapy, laser photocoagulation, and sham injection. Most trials had an overall unclear or high risk of bias. One trial (701 eyes ) compared intravitreal dexamethasone implant 0.7mg with sham. We found moderate‐certainty evidence that dexamethasone leads to slightly more improvement of visual acuity than sham at 12 months (mean difference [MD] −0.08 logMAR, 95% confidence interval [CI] −0.12 to −0.05 logMAR). Regarding improvement of three or more lines of visual acuity, there was moderate‐certainty evidence in favor of dexamethasone at 12 months, but the CI covered the null value (risk ratio (RR) 1.39, 95% CI 0.91 to 2.12). Regarding adverse events, dexamethasone increased by about four times the risk of cataract progression and the risk of using intraocular pressure (IOP)‐lowering medications compared to sham (RR 3.89, 95% CI 2.75 to 5.50 and RR 4.54, 95% CI 3.19 to 6.46, respectively; moderate‐certainty evidence); about 4 in 10 participants treated with dexamethasone needed IOP‐lowering medications. Two trials (451 eyes) compared intravitreal dexamethasone implant 0.7mg with intravitreal antiVEGF (bevacizumab and ranibizumab). There was moderate‐certainty evidence that visual acuity improved slightly less with dexamethasone compared with antiVEGF at 12 months (MD 0.07 logMAR, 95% CI 0.04 to 0.09 logMAR; 2 trials; 451 participants/eyes; I(2) = 0%). The RR of gain of three or more lines of visual acuity was inconsistent between trials, with one trial finding no evidence of a difference between dexamethasone and bevacizumab at 12 months (RR 0.99, 95% CI 0.70 to 1.40; 1 trial; 88 eyes), and the other, larger trial finding the chances of vision gain were half with dexamethasone compared with ranibizumab (RR 0.50, 95% CI 0.32 to 0.79; 1 trial; 432 participants). The certainty of evidence was low. Cataract progression and the need for IOP‐lowering medications increased more than 4 times with dexamethasone implant compared to antiVEGF (moderate‐certainty evidence). One trial (560 eyes) compared intravitreal fluocinolone implant 0.19mg with sham. There was moderate‐certainty evidence that visual acuity improved slightly more with fluocinolone at 12 months (MD −0.04 logMAR, 95% CI −0.06 to −0.01 logMAR). There was moderate‐certainty evidence that an improvement in visual acuity of three or more lines was more common with fluocinolone than with sham at 12 months (RR 1.79, 95% CI 1.16 to 2.78). Fluocinolone also increased the risk of cataract progression (RR 1.63, 95% CI 1.35 to 1.97; participants = 335; moderate‐certainty evidence), which occurred in about 8 in 10 participants, and the use of IOP‐lowering medications (RR 2.72, 95% CI 1.87 to 3.98; participants = 558; moderate‐certainty evidence), which were needed in 2 to 3 out of 10 participants. One small trial with 43 participants (69 eyes) compared intravitreal triamcinolone acetonide injection 4 mg with sham. There may be a benefit in visual acuity at 24 months (MD −0.11 logMAR, 95% CI −0.20 to −0.03 logMAR), but the certainty of evidence is low. Differences in adverse effects were poorly reported in this trial. Two trials (615 eyes) compared intravitreal triamcinolone acetonide injection 4mg with laser photocoagulation and reached discordant results. The smaller trial (31 eyes followed up to 9 months) found more visual acuity improvement with triamcinolone (MD −0.18 logMAR, 95% CI −0.29 to −0.07 logMAR), but a larger, multicenter trial (584 eyes, 12‐month follow‐up) found no evidence of a difference regarding change in visual acuity (MD 0.02 logMAR, 95% CI ‐0.03 to 0.07 logMAR) or gain of three or more lines of visual acuity (RR 0.85, 95% CI 0.55 to 1.30) (overall low‐certainty evidence). Cataract progression was about three times more likely (RR 2.68, 95% CI 2.21 to 3.24; moderate‐certainty evidence) and the use of IOP‐lowering medications was about four times more likely (RR 3.92, 95% CI 2.59 to 5.96; participants = 627; studies = 2; I(2) = 0%; moderate‐certainty evidence) with triamcinolone. About 1 in 3 participants needed IOP‐lowering medication. One small trial (30 eyes) compared intravitreal triamcinolone acetonide injection 4mg with intravitreal antiVEGF (bevacizumab or ranibizumab). Visual acuity may be worse with triamcinolone at 12 months (MD 0.18 logMAR, 95% CI 0.10 to 0.26 logMAR); the certainty of evidence is low. Adverse effects were poorly reported in this trial. Four trials reported data on pseudophakic participants, for whom cataract is not a concern. These trials found no decrease in visual acuity in the second treatment year due to cataract progression. AUTHORS' CONCLUSIONS: Intravitreal steroids may improve vision in people with DME compared to sham or control. Effects were small, about one line of vision or less in most comparisons. More evidence is available for dexamethasone or fluocinolone implants when compared to sham, and the evidence is limited and inconsistent for the comparison of dexamethasone with antiVEGF treatment. Any benefits should be weighed against IOP elevation, the use of IOP‐lowering medication and, in phakic patients, the progression of cataract. The need for glaucoma surgery is also increased, but remains rare