Screening for Diabetic Retinopathy Using an Automated Diagnostic System Based on Deep Learning: Diagnostic Accuracy Assessment.

PURPOSE: To evaluate the diagnostic accuracy of a diagnostic system software for the automated screening of diabetic retinopathy (DR) on digital colour fundus photographs, the 2019 Convolutional Neural Network (CNN) model with Inception-V3. METHODS: In this cross-sectional study, 295 fundus images were analysed by the CNN model and compared to a panel of ophthalmologists. Images were obtained from a dataset acquired within a screening programme. Diagnostic accuracy measures and respective 95% CI were calculated. RESULTS: The sensitivity and specificity of the CNN model in diagnosing referable DR was 81% (95% CI 66-90%) and 97% (95% CI 95-99%), respectively. Positive predictive value was 86% (95% CI 72-94%) and negative predictive value 96% (95% CI 93-98%). The positive likelihood ratio was 33 (95% CI 15-75) and the negative was 0.20 (95% CI 0.11-0.35). Its clinical impact is demonstrated by the change observed in the pre-test probability of referable DR (assuming a prevalence of 16%) to a post-test probability for a positive test result of 86% and for a negative test result of 4%. CONCLUSION: A CNN model negative test result safely excludes DR, and its use may significantly reduce the burden of ophthalmologists at reading centres.

Paracentral acute middle maculopathy-review of the literature.

Paracentral acute middle maculopathy (PAMM) is a recently identified spectral-domain optical coherence tomography (SD-OCT) finding characterized by a hyper-reflective band spanning the inner nuclear layer (INL), which typically evolves to INL atrophy in later stages. Typical clinical features include the sudden onset of one or multiple paracentral scotomas, normal or mild reduction in visual acuity, and a normal fundus appearance or a fundus with a deep grayish lesion. Although its pathophysiology is not yet fully understood, ischemia at the level of the intermediate and deep capillary plexa has been demonstrated to play a major role. Since its first description, an increasing number of publications on PAMM have been published in ophthalmology scientific journals. The purpose of this study is to provide a review of the current literature on PAMM.

Rho kinase inhibitors-a review on the physiology and clinical use in Ophthalmology.

The Rho kinase (ROCK) signaling pathway is involved in several cellular events that include cell proliferation and cytoskeleton modulation leading to cell adhesion. The ROCK pathway in the human eye has been hypothesized to play important roles in corneal endothelial cell physiology and pathologic states. In addition, ROCK signaling has been identified as an important regulator of trabecular meshwork (TM) outflow, which is altered in glaucomatous eyes. These roles in corneal and glaucomatous disease states have led to the growing interest in the development of drugs selectively targeting this pathway (ROCK inhibitors). The authors provide a review of the literature on the pathobiology of the ROCK signaling in corneal endothelial disease, glaucoma, and vitreoretinal disease, as well as the clinical usefulness of ROCK inhibitors in Ophthalmology.

Outer Retina and Choroidal Thickness in Intermediate Age-Related Macular Degeneration: Reticular Pseudodrusen Findings.

PURPOSE: To evaluate outer retina and choroidal thickness in subjects with intermediate age-related macular degeneration (iAMD) and to describe associations with the presence of reticular pseudodrusen (RPD). METHODS: This was a retrospective, cross-sectional analysis of 157 consecutive eyes (specifically: 62 eyes classified as having RPD and 95 eyes with drusen ≥125 µm). Only cases with digital color fundus photographs, red-free, and infrared, obtained and graded according to the Age-Related Eye Disease Study to define iAMD, were used for this study. Outer retina and choroidal thickness were manually segmented and quantified at 12 locations in the horizontal meridian. RESULTS: RPD appeared to be associated with thinning of the outer layers even after adjustment for gender and age. The presence of RPD in iAMD decreased with increase of choroidal thickness (total odds ratio [OR] 0.991, 95% confidence interval [CI] 0.985-0.996; nasal OR 0.992, 95% CI 0.986-0.997), with increased thickness of the myoid zone of the photoreceptors (total OR 0.812, 95% CI 0.688-0.958; nasal OR 0.863, 95% CI 0.755-0.987) and with increased thickness of the outer segment of the photoreceptors (total OR 0.850, 95% CI 0.731-0.989; nasal OR 0.857, 95% CI 0.736-0.989). CONCLUSIONS: The greatest differences between eyes with and without RPD are found at the level of the choroidal thickness and at the level of the photoreceptors.

Ganglion Cell Complex in Early and Intermediate Age-Related Macular Degeneration: Evidence by SD-OCT Manual Segmentation.

PURPOSE: To evaluate ganglion cell layer (GCL) and ganglion cell complex (GCC) thickness manually by spectral-domain optical coherence tomography in subjects with early and intermediate age-related macular degeneration (AMD) in 12 locations on the horizontal meridian. METHODS: A total of 450 eyes (specifically, 246 eyes classified as having early/intermediate AMD plus 204 control eyes) were studied. Mann-Whitney U and Kruskal-Wallis tests were used to compare values between the healthy controls and the AMD group and also between the subgroups under study. Diagnostic performance was also compared calculating the areas under the receiver operating characteristic curve. RESULTS: The manual layer segmentation showed clear boundaries between the GCL and the GCC. It was in the temporal GCC that more changes were found. CONCLUSIONS: The GCC, especially in the temporal region, allowed the discrimination of differences between various subgroups that have faint variations as well as between early AMD and the first signs of aging.

First Incidence and Progression Study for Diabetic Retinopathy in Portugal, the RETINODIAB Study: Evaluation of the Screening Program for Lisbon Region.

PURPOSE: To estimate the 5-year incidence and progression of diabetic retinopathy (DR) among persons with type 2 diabetes mellitus (DM). DESIGN: Population-based, prospective, cohort study. PARTICIPANTS: The RETINODIAB (Study Group for Diabetic Retinopathy Screening) program was implemented in the Lisbon and Tagus Valley area between July 2009 and December 2014. A total of 109 543 readable screening examinations were performed and corresponded to 56 903 patients who attended the screening program at entry. A total of 30 641 patients (53.85%) had at least 1 further screening event within the study period and were included in the analysis. METHODS: Participants underwent two 45° nonstereoscopic retinal digital photographs per eye according to RETINODIAB protocol. All images were graded according to the International Clinical Diabetic Retinopathy Scale. Referable diabetic retinopathy (RDR) was defined for all patients graded as moderate nonproliferative DR (NPDR), severe NPDR, or proliferative DR (PDR), with or without maculopathy or mild NPDR with maculopathy. Nonparametric estimates of the annual and cumulative incidences were obtained by Turnbull's estimator. Associations between the potential risk factors and the time to onset/progression of retinopathy were assessed through a parametric survival analysis for interval-censored data. MAIN OUTCOME MEASURES: The authors estimated the onset and progression incidence rates of DR. RESULTS: Yearly incidence of any DR in patients without retinopathy at baseline was 4.60% (95% confidence interval [CI], 3.96-4.76) in the first year, decreasing to 3.87% (95% CI, 2.57-5.78) in the fifth year. In participants with mild NPDR at baseline, the progression rate to RDR in year 1 was 1.18% (95% CI, 0.96-1.33). Incidence of any DR and RDR and DR progression rate were associated with known duration of diabetes, age at diagnosis, and use of insulin treatment. CONCLUSIONS: This longitudinal epidemiologic study provides the first Portuguese incidence DR data in a large-scale population-based cohort of type 2 diabetes after a 5-year follow-up. Duration of diabetes, age at diagnosis, and insulin treatment were associated with increasing risk of incidence and progression of DR. A personalized schedule distribution of screening intervals according to the individual patient's profile should be implemented, with resulting benefits in terms of health costs.

Anatomical and visual outcomes in high myopic macular hole (HM-MH) without retinal detachment: a review.

PURPOSE: To review postoperative anatomical and functional outcomes in high myopic macular hole (HM-MH) without retinal detachment. METHODS: In the PubMed database, published articles on myopic macular hole surgery from 2000 to 2013 (present days) were reviewed. Inclusion criteria were high myopia and macular hole (MH). Series with posterior retinal detachment secondary to MH and myopic foveoschisis (MFS) without MH were excluded. Main outcomes included MH closure rate, resolution of the foveoschisis, if present, and postoperative visual acuity. Optical coherence tomography (OCT) features and postoperative evolution were also evaluated when reported. RESULTS: A total of 131 articles were initially found. After having applied the exclusion criteria, 15 articles were reviewed. Four were focused on HM-MH with concomitant foveoschisis (Schisis Group), and ten included only HM-MH without FS case series (Flat Group). Only one comparative study between these two groups was found. Surgical techniques were observed to be similar for both groups in most series, including vitrectomy with or without internal limiting membrane (ILM) removal, and gas or silicone oil tamponade. However, in one retrospective study, macular buckling was applied together with pars plana vitrectomy in cases of HM-MH with foveoschisis. When available, preoperative and postoperative OCT provided a useful evaluation of the status of the macula. Different prognosis were observed in the two groups in cases of vitreous surgery: anatomical success rate and functional outcomes for HM-MH with foveoschisis were markedly poorer than that for cases of HM-MH without foveoschisis, and multiple procedures might be required. By the contrast, better results seemed to be achieved using the posterior buckle technique for patients with HM-MH and concomitant foveoschisis. Moreover, when compared, final anatomical and functional outcomes seem to be less satisfactory than in emmetropic eyes. Postoperative non-closure or reopening of the macular hole is more common in eyes with HM-MH and concomitant foveoschisis, and possible retinal detachment may occur in these patients. CONCLUSIONS: Despite similar surgical procedures, anatomical and functional results after vitreous surgery in cases of HM-MH may be very different from series to series. The prognosis is generally better in cases involving only HM-MH without foveoschisis than in cases with MH and associated foveoschisis. Persistent MHs are more frequent in eyes with concomitant retinoschisis, and this seems to represent a possible risk factor for late retinal detachment in the case of unsuccessful vitreous surgery. However, although vitrectomy can lead to anatomical and visual improvements, an higher axial length > 30 mm and the presence of a posterior staphyloma seem to remain the two most important risk factors for poor visual outcomes. For these reasons, a different surgical approach, including macular buckling, might be considered in casse of HM-MH and concomitant myopic foveoschisis, in order to counteract the traction exerted by the posterior staphyloma.

Dexamethasone intravitreal implant for treatment of patients with persistent diabetic macular edema.

PURPOSE: To report the 6-month anatomical and best-corrected visual acuity (BCVA) response after primary intravitreal dexamethasone implantation (Ozurdex®) in patients with refractory diabetic macular edema (DME). METHODS: Retrospective review of the medical records of 58 patients with decreased visual acuity, due to refractory DME, who underwent a single injection of Ozurdex between November 2010 and January 2012, at the Instituto de Microcirurgia Ocular, Barcelona, Spain. RESULTS: At baseline, the mean foveal thickness (FT) was 543.24 ± 156.51 µm. Mean (±SD) values of FT did decrease to 346.82 ± 123.74 µm at month 1 and 341.12 ± 129.64 µm at month 3. Data on the 6-month follow-up showed a mild increase to 420.16 ± 152.15 µm. All of the FT reduction outcomes were statistically significant, with respect to baseline data (p = 0.0001). The baseline BCVA data was 0.66 ± 0.36 logarithm of the minimum angle of resolution (logMAR). The mean BCVA improved to 0.52 ± 0.32 logMAR (p = 0.0001) and 0.44 ± 0.27 logMAR (p = 0.0001) after 1 and 3 months, respectively. At the last visit (6-month follow-up), the mean BCVA increased to 0.51 ± 0.31 logMAR (p = 0.0001). CONCLUSIONS: In this study, intravitreal treatment with a dexamethasone implant safely reduced DME and improved visual acuity in a difficult-to-treat patient population with long-standing refractory DME.

Surgical approach for management of complete anterior capsular contraction syndrome.

Anterior capsular contraction syndrome is an uncommon but well-known complication associated with continuous curvilinear capsulorhexis performed during cataract surgery. It remains asymptomatic unless the constriction progresses to involve the visual axis or causes late intraocular lens-related complications. A male patient in his 50s presented with severely decreased vision in his right eye 2 years after uneventful cataract surgery. Slit-lamp biomicroscopy revealed capsular phimosis and a dense, central, fibrous plaque with total occlusion of the anterior capsulorhexis opening. Neodymium-doped yttrium aluminium garnet laser anterior capsulotomy and vitrectorhexis were attempted, but proved ineffective. Surgical excision with manual cutting of the fibrotic membrane was performed, successfully clearing the visual axis and restoring vision.

Intraocular Lens Opacification After Descemet's Membrane Endothelial Keratoplasty-Risk Factors and Outcomes After Intraocular Lens Exchange.

PURPOSE: To determine risk factors for intraocular lens opacification (IOLop) after Descemet membrane endothelial keratoplasty (DMEK) and to analyze clinical outcomes after IOL exchange. METHODS: Cross-Sectional Study: Analysis of all cases of IOL exchange because of post-DMEK IOLop with a minimum of 6-month postoperative follow-up observed in clinic between November 2021 and April 2022. Main outcomes analyzed at the study visit were change in logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity after IOL exchange, endothelial cell loss (ECL), and graft survival. An historical cohort of 232 pseudophakic DMEK eyes was retrospectively analyzed to determine risk factors for post-DMEK IOLop. RESULTS: Cross-Sectional Study: Four eyes were observed (median follow-up = 45 (35.5-86.8) months). IOL materials were hydrophilic acrylic IOLs in 2 eyes and hydrophobic-hydrophilic in the other 2. At the study visit, improvement in median best-corrected visual acuity after IOL exchange was statistically significant (0.25 (0.19-0.41) logMAR to 0.00 (0-0.10) logMAR; P = 0.041). ECL ranged between 57.7% and 85.3%, without cases of graft failure. In the historical cohort, 21 eyes (9.05%) had some IOLop. In multivariate logistic regression model (105 eyes where IOL material data was available), IOLs with high water content material (odds ratio = 65.5, P = 0.0005) and rebubbling (odds ratio = 9.51, P = 0.0138) were independent risk factors for post-DMEK IOLop. CONCLUSIONS: Post-DMEK IOLop is infrequent, but a non-neglectable proportion of cases may require IOL explantation. IOL exchange is safe and effective in these eyes but may pose a risk for increased ECL. This study confirms that IOL material and number of rebubblings are major risk factors for post-DMEK IOLop.

Descemet's Membrane Endothelial Keratoplasty for Corneal Endothelial Failure Secondary to Three Types of Phakic Intraocular Lens - Retrospective Study.

Purpose: To analyze the outcomes of Descemet's membrane endothelial keratoplasty (DMEK) for corneal endothelial failure secondary to phakic intraocular lens implantation (PIOL) at a reference center for corneal transplantation in Spain. Design: Retrospective, single-surgeon case series. Methods: Single-center analysis of patients who underwent DMEK for PIOL-related corneal decompensation between July 2011 and July 2020 with at least 6 months of follow-up postoperatively. Primary outcome was final best-corrected visual acuity (BCVA, logMAR) compared to pre-DMEK BCVA. Secondary outcomes analyzed included post-DMEK refractive spherical equivalent, endothelial cell loss (%ECL), and graft failure. Results: Sixteen eyes (14 patients) underwent DMEK for PIOL-related corneal decompensation. Mean (SD) time to PIOL explantation was 9.3 (5.0) years, and median (P25-P75) time between PIOL explantation and DMEK surgery was 3 (2-4) months. Median pre-DMEK BCVA was 0.80 (1.08-0.60) logMAR. A statistically significant improvement in BCVA was observed 1 month after DMEK (p = 0.001), and median final BCVA was 0.15 (0.0-0.35) logMAR (p = 0.002). Mean %ECL was 55.6 (18.7) % at 2-year follow-up and 61.7 (11.7) % in eyes with over 4 years of follow-up. Two eyes required re-bubbling (12.5%), one of which ended in primary graft failure (6.2%) and one eye had late endothelial graft failure (LEGF) at 4-year follow-up (1/15 grafts, 6.7%). Conclusion: In patients with PIOL-related corneal decompensation, DMEK leads to good and clinically significant refractive and visual outcomes in the medium-long term, with a good safety profile. Prospective studies are encouraged to ascertain whether these cases are at increased risk of accelerated endothelial cell loss and LEGF.

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response.

PURPOSE: DNA methylation is involved in Diabetic Retinopathy progression showing a metabolic memory mechanism. However, the association of DNA methyltransferase with diabetic macular edema is still unknown. We aimed to describe the differences in DNA methyltransferase gene expression in patients with different diabetic macular edema responses. METHODS: A total of 27 diabetic patients, aged 59-90 years, were prospectively enrolled in this cross-sectional study. The participants were classified into control group (CG, n = 11), diabetic macular edema responders (rDME, n = 9) and non-responder diabetic macular edema (nrDME, n = 7) after anti-vascular endothelial growth factor (anti-VEGF) treatment. Only cases with a complete ophthalmological examination, digital 133° color fundus, and SD-OCT assessments were used. After RNA extraction and first-strand cDNA synthesis, quantitative real-time PCR was performed with specific primers on the CFX Connect™ Real-Time PCR Detection System to assess differential transcriptional expression patterns. RESULTS: The DNMT1 gene showed a positive correlation (r = 0.617; p = 0.043) with Best Corrected Visual Acuity (BCVA) in CG, a positive correlation (r = 0.917; p = 0.010) with HbA1c in nrDME and a negative correlation (r = -0.659; p = 0.049) with GCL-IPL thickness in rDME. DNMT3A gene showed a positive correlation (r = -0.890; p = 0.001) with Sub-foveal Choroidal thickness in rDME whereas DNMT3b gene showed a negative correlation (r = -0.815; p = 0.007) with HbA1c and RNFL (r = -0.664; p = 0.026) in CG. CONCLUSIONS: Patients with similar metabolic profile risk factors showed associated DNA methyltransferase transcriptional expression patterns differences fitting with the anti-VEGF diabetic macular edema response. Further studies are needed to clarify if these results (1) reflect disease evolution, (2) translate the therapeutic impact, (3) or can help to predict the therapeutic resistance profile.

Manual Segmentation of 12 Layers of the Retina and Choroid through SD-OCT in Intermediate AMD: Repeatability and Reproducibility.

PURPOSE: To evaluate the repeatability and reproducibility of the segmentation of 12 layers of the retina and the choroid, performed manually by SD-OCT, along the horizontal meridian at three different temporal moments, and to evaluate its concordance with the same measurements performed by two other operators in intermediate AMD. METHODS: A cross-sectional study of 40 eyes from 40 subjects with intermediate AMD was conducted. The segmentation was performed manually, using SD-OCT. The 169 measurements per eye were repeated at three time points to study the intra-operator variability. The same process was repeated a single time by two different trained operators for the inter-operator variability. RESULTS: Forty participants (28 women and 12 men) were enrolled in this study, with an average age of 76.4 ± 8.2 (range, 55-92 years). Overall, the maximum values of the various structures were found in the 3 mm of the macula. Intra-operator variability: the highest ICC values turned out to be discovered in thicker locations. Inter-operator variability: except correlation values of 0.826 (0.727; 0.898) obtained in the OPL (T2.5) and 0.634 (0.469; 0.771) obtained in the IPL (N2), all other correlation values were > 0.92, in most cases approaching higher values like 0.98. CONCLUSION: The measurements of several layers of the retina and the choroid achieved at 13 locations presented a good repeatability and reproducibility. Manual quantification is still an alternative for the weaknesses of automatic segmentation. Locations of greatest concordance should be those used for the clinical control and monitoring.

Dexamethasone intravitreal implant (Ozurdex) in diabetic macular edema: real-world data versus clinical trials outcomes.

AIM: To investigate the safety and efficacy of intravitreal dexamethasone implants (Ozurdex®/DEX) in patients with diabetic macular edema (DME) either naïve or non-naïve to anti-VEGF therapies who switched to DEX implant independent of response to anti-vascular endothelial growth factors (anti-VEGFs). METHODS: This was an audit retrospective review of medical records of patients with DME who switched to the DEX intravitreal implant. Patients were divided into 2 groups: patients naïve to antiangiogenic therapy and patients who were previously treated with anti-VEGFs. Data regarding demographics, changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) was collected over 6mo. The demographic data mean changes in BCVA, CMT, and IOP were compared. Six-month follow-up data of 47 patients (57 eyes), who either switched to DEX implant irrespective of response to previous treatments or were treatment naïve before receiving DEX implant, was collected. RESULTS: Improvement in mean BCVA was observed from 1-4mo after injection with a decreased effect at month 6 as expected, with better outcomes in naïve compared to non-naïve patients. A statistically relevant decrease in mean CMT was observed during the follow-up period. An increase in mean IOP was observed in the first 2mo after DEX therapy. The mean number of injections of the overall population during the 6mo was 1.3. A subgroup analysis showed no relevant difference between phakic versus pseudophakic patients relative to measured outcomes. There was no cataract progression during the follow-up period and no adverse events reported. CONCLUSION: This real-life setting study shows that intravitreal DEX implant is effective and safe. The timings of greater therapeutic impact are concordant with previous studies and suggest that earlier treatment with corticosteroids may have an additional benefit in naïve patients.

Secondary Epiretinal Membrane After Trabeculectomy.

PURPOSE: To determine the frequency of epiretinal membranes (ERM) in eyes with primary open-angle glaucoma subjected to trabeculectomy. METHODS: We conducted a retrospective study on patients subjected to trabeculectomy with at least a 6-month follow-up. Ophthalmologic examination and spectral-domain optical coherence tomography (SD-OCT) were analyzed. Eyes with previous surgical or laser treatments or other pathologies (other than glaucoma and ERM) were excluded. RESULTS: A total of 50 eyes (40 patients) were included in this study. The mean follow-up time after surgery was 27.8 months. After surgery, 9 eyes (18%) had preretinal macular fibrosis and 19 eyes (38%) had cellophane macular reflex. Of the 16 eyes with a preoperative macular SD-OCT, 3 (18.8%) developed ERM and 4 (25%) progressed from cellophane macular reflex to preretinal macular fibrosis, after surgery. The ERM frequency did not differ significantly between eyes subjected to trabeculectomy with or without the use of antimetabolites (P=0.08), or between eyes subjected to simple or combined surgery (phacotrabeculectomy) (P=0.09). CONCLUSION: Trabeculectomy may predispose one to the appearance and progression of ERM. Further studies are needed to clarify this intriguing relation.

Full-thickness macular hole after lamellar macular hole surgery: a case report.

PURPOSE: To describe a case of full-thickness macular hole (FTMH) after vitrectomy for lamellar hole (LH). METHODS: Case report. RESULTS: The authors report a patient with progressive visual loss secondary to LH who developed FTMH following a vitrectomy repair. The postoperative findings as well as the clinical course after the second surgical approach are described. CONCLUSIONS: Surgeons should be aware of this complication following LH surgical approach.