Eyes that Do Not Meet the Eligibility Criteria of Clinical Trials on Age-Related Macular Degeneration: Proportion of the Real-World Patient Population and Reasons for ExclusionRead the full article
Journal of Ophthalmology publishes original research articles, review articles, and clinical studies related to the anatomy, physiology and diseases of the eye.
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Clinical Features, Prognosis, and Long-Term Response to Ranibizumab of Macular CNVs in Pattern Dystrophies Spectrum: A Pilot Study
Introduction. To analyze the morphological and functional features of choroidal neovascularizations (CNVs) in eyes affected by pattern dystrophies (PD), evaluating their long-term response to intravitreal ranibizumab, and comparing them with CNVs in age-related macular degeneration (AMD). The mean goal is to identify possible disease biomarkers and to evaluate the long-term prognosis of CNVs in PD. Materials and Methods. A retrospective study of 42 patients with naïve CNV (26 PD and 16 AMD), for a total of 47 eyes (29 eyes in the PD group and 18 eyes in the AMD group). Each patient received a loading dose of ranibizumab (one monthly for three months) followed by pro re nata (PRN) reinjection protocol for a period of at least three years. Morphological OCT parameters (CRT, central retinal thickness; SRF, subretinal fluid; IRF, intraretinal fluid; SHRM, subretinal hyperreflective material; HRF, hyperreflective foci; HCD, hyperreflective crystalline deposits; cCT, central choroidal thickness; slCT, sublesional choroidal thickness; EZd, ellipsoid zone disruption; and best corrected visual acuity (BCVA in logMAR scale)) were reported at baseline and last follow-up. Results. At baseline, no significant differences were found between the two groups, except for choroidal thickness parameters that were significantly greater in the PD group ( = 0.009). Longitudinal PD analysis demonstrated reduction in BCVA ( = 0.009), decrease in CRT ( = 0.046), resolution of SRF in 61.6% of cases ( = 0.004) and SHRM in 30% ( = 0.034), and choroidal thinning both centrally ( = 0.004) and sublesional ( = 0.011) compared to baseline. At 3 years, the PD group received significantly more injections than the AMD ( = 0.011) and showed significantly thicker choroid ( = 0.033) and more frequent HRF ( = 0.006). Regarding the PD group, we found a negative correlation between age and choroidal thicknesses at baseline and at 3 years ( < 0.05); significant positive correlations were found between baseline BCVA and at 3 years ( < 0.001), BCVA at 3 years and IRF ( = 0.003) and SHRM at 3 years ( = 0.003); CRT baseline and CRT 3 years ( = 0.017); HCD at 3 years was associated with greater CRT ( = 0.04) and IRF at 3 years ( = 0.019). Conclusions. Early and long-term morphofunctional features of CNVs in PD and in AMD are overlapping. CNVs in PD have poorer long-term response to ranibizumab and higher choroidal thickness suggesting different pathogenetic and evolutionary mechanisms.
Intravitreal Dexamethasone Implant for Postoperative Macular Oedema Secondary to Vitrectomy for Epiretinal Membrane and Retinal Detachment: A Systematic Review and Meta-Analysis
Purpose. To evaluate the efficacy of intravitreal dexamethasone implant (DEX) for the treatment of macular oedema secondary to vitrectomy for epiretinal membrane (ERM) and retinal detachment (RD) by conducting a systematic review with meta-analysis of published studies. Methods. Studies reporting clinical outcomes of DEX use for the treatment of macular oedema secondary to ERM and RD vitrectomy were searched on PubMed and Embase databases. The primary outcome was best-corrected visual acuity (BCVA) change between baseline and post-DEX treatment, reported as mean difference (MD) with 95% confidence interval (CI). Mean central macular thickness (CMT) change was assessed as a secondary outcome. Postimplant adverse events, including intraocular pressure rise and cataract development, were reported as well. Results. Five uncontrolled studies, 1 nonrandomized controlled study, and 1 randomized controlled study were included, with a total of 5 cohorts and 3 cohorts in the ERM group and RD group, respectively. Considering the last available follow-up, a significant improvement in postimplant BCVA was found in the overall population, irrespective of the indication for vitrectomy (MD = −0.28, 95% CI = −0.37, −0.20; ), but with significant heterogeneity. In either group, mean BCVA significantly improved following the implant (in the ERM group, MD = −0.31, 95% CI = −0.40, −0.22; in the RD group, MD = −0.22, 95% CI = −0.41, −0.03), with no difference between the two groups (). However, there was significant heterogeneity in both groups. Considering the last available follow-up, a significant CMT reduction was found in the overall population, irrespective of the indication for vitrectomy (MD = −129.75, 95% CI = −157.49, −102.01; ). In the ERM group, a significant CMT reduction was shown following DEX (MD = −133.41, 95% CI = −155.37, −111.45; ), with no heterogeneity. In the RD group, mean CMT reduction was borderline significant (MD = −128.37, 95% CI = −253.57, −3.18; ), with significant heterogeneity. No difference in CMT improvement was found between the two groups (). Conclusion. This meta-analysis showed that DEX yielded a significant improvement in visual and anatomical outcomes, even if limited by significant heterogeneity. Dexamethasone implant represents an effective treatment for postoperative macular oedema secondary to ERM and RD vitrectomy.
The Role of Intravitreal Anti-VEGF Agents in Rabbit Eye Model of Open-Globe Injury
Purpose. To evaluate the effects of intravitreal anti-VEGF agents in a rabbit model of open-globe injury (OGI). Methods. OGI was induced in the right eyes of 75 Belgian rabbits by making 5 mm circumferential incision placed 6 mm behind the limbus. The rabbits were divided into 4 groups: control (n = 5), OGI group (n = 40), and intravitreal Ranibizumab and Conbercept (n = 15 each). Ranibizumab or Conbercept was injected into the vitreous at 0.5 hours, 3 days, or 7 days. Vitreous fluid was collected, and levels of growth factors and cytokines were measured by enzyme-linked immunosorbent assay (ELISA). On day 28 after OGI, B scan examination and histological examination were performed to evaluate intravitreal proliferation and formation of epiretinal fibrosis. Results. Vitreous levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and plasminogen activator inhibitor-1 (PAI-1) were significantly increased in rabbit eyes after OGI. Compared to eyes in OGI group, anti-VEGF treatments significantly reduced these growth factors and cytokines. Among the 7 eyes examined from each group for intravitreal proliferative changes, they were found in 7 of 7 (100%) in OGI group and were decreased by Ranibizumab and Conbercept to 5 of 7 (71.4%) and 4 of 7 (57.1%), respectively. Both Ranibizumab and Conbercept inhibited epiretinal scar formation at the wound site, with Conbercept showing the greatest effect (maximal length of scar (L), LOGI = 503 ± 82.44 μm, LRanibizumab = 355 ± 43.66 μm, and LConbercept = 250.33 ± 36.02 μm). Conclusion. Anti-VEGF treatments after OGI significantly attenuated the upregulation of growth factors and cytokines in the vitreous and prevented intravitreal proliferation and epiretinal scar formation and thus may protect against the development of posttraumatic complications such as proliferative vitreoretinopathy (PVR).
Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma
The exact mechanism of retinal ganglion cell loss in the pathogenesis of glaucoma is yet to be understood. Mitochondrial damage-associated molecular patterns (DAMPs) resulting from mitochondrial dysfunction have been linked to Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy, as well as to brain neurodegenerative diseases. Recent evidence shows that, in conditions where mitochondria are damaged, a sustained inflammatory response and downstream pathological inflammation may ensue. Mitochondrial damage has been linked to the accumulation of age-related mitochondrial DNA mutations and mitochondrial dysfunction, possibly through aberrant reactive oxygen species production and defective mitophagy. The present review focuses on how mitochondrial dysfunction may overwhelm the ability of neurons and glial cells to adequately maintain homeostasis and how mitochondria-derived DAMPs trigger the immune system and induce neurodegeneration.
Isolated Central Epiretinal Membrane: A Rare Complication of Fovea-Sparing Internal Limiting Membrane Peeling Technique
Purpose. To report a rare complication presenting as an isolated central epiretinal membrane (ERM) related to fovea-sparing internal limiting membrane (ILM) peeling technique. Methods. Five patients who received fovea-sparing ILM peeling were enrolled. Postoperatively, an isolated central ERM developed. Optical coherence tomography (OCT) was used to evaluate the serial anatomic change. Results. Among the five included patients, one patient had high myopia with foveoschisis, two patients had vitreomacular traction, and two patients had proliferative diabetic retinopathy with tractional retinal detachment and a fovea cyst. With an average of 5.80 months, OCT showed the gradual development of the isolated central ERM with severe fovea distortion. Four patients received secondary revision surgery, with improvement of the fovea contour and visual acuity. Conclusion. The fovea-sparing ILM peeling technique may cause a rare but serious complication as the isolated central ERM, which would cause significant fovea distortion as well as visual deterioration. Timely detection and intervention is recommended to prevent further visual loss. This trial is registered with NCT04445142.
Determination of Ischemia Onset Based on Automatically Generated Spectralis SD-OCT Values in Acute Central Retinal Artery Occlusion
Acute central retinal artery occlusion (CRAO) induces a time-dependent increase in retinal thickness. By manually measuring the relative retinal thickness increase (RRTI) in comparison to the contralateral eye based on optical coherence tomography (OCT), ischemia onset within the past 4.5 hours could be determined with 100% sensitivity and 94.3% specificity. To enable examiner-independent and quicker diagnostics, we analyzed the RRTI using the automatic retinal thickness measurement. In this retrospective study, 28 eyes were evaluated with an acute CRAO (<46 hours). All patients received a Spectralis SD-OCT image of both eyes. The RRTI was calculated for the ETDRS sectors using the Segmentation Module for Single Retinal Layer Analysis. Receiver operating characteristic (ROC) analysis was performed to determine patients ≤4.5 hours by RRTI. In all sectors, time to OCT (TTO) and RRTI correlated positively. The optimal cutoff point to detect CRAOs ≤4.5 hours was between 18.7% nasally and 22.9% RRTI temporally. Sensitivity and specificity varied between the sectors with 90–95% sensitivity and 89–100% specificity. In conclusion, the automatic measurement of RRTI also allows the differentiation of CRAOs within a possible therapeutic time window ≤4.5 hours and CRAOs ≥4.5 hours with a high sensitivity and specificity. Additionally, it offers quicker, easier, and a user-independent assessment of ischemia onset, helping to set a base for establishing automatic indices generated by the OCT machines.