Reproducibility of SIMPLE classification for diabetic retinopathy screening and its comparison to current Italian guidelines.

PURPOSE: To evaluate the reproducibility of SIMPLE (Single field Image Multi Parameters defined Lesions Extent), a new Diabetic Retinopathy (DR) classification for screening of 45° single field fundus pictures of patients with diabetes (PwDM), assessing DR, Diabetic Maculopathy (DMac) and referral rate agreement and comparing it to current Italian Guidelines (IG). MATERIALS AND METHODS: We conducted a retrospective, observational, multicentre study, collecting 1000 retinal 45° single field images of PwDM obtained during routine visits in two diabetes clinics. Three ophthalmologists evaluated each image, determining the presence and number of specific DR lesions and then assigning a stage according to the current IG for screening. SIMPLE staging was performed automatically via Excel software, based on the pre-specified DR characteristics observed by the graders. We analysed intra-centre, inter-centre and total inter-grader agreement for DR and DMac stage and referral rate of the two classifications. RESULTS: Agreement amongst the three graders was consistently higher when using SIMPLE classification than when using current IG classification. For DR, kappa (k) was 0.86 with IG and 0.95 with SIMPLE classification; for DMac, k-IG was 0.78, while k-SIMPLE was 0.96; concordance on the referral rate was 0.91 with IG and 0.99 with SIMPLE. Similar results were obtained in sub-analyses for the evaluation of intra-centre and inter-centre concordance. CONCLUSIONS: Our results suggest that the new SIMPLE classification has an excellent reproducibility amongst graders, comparable or superior to the current IG for DR screening proposed in 2015, improving the standardisation of the decision on referability.

Optical coherence tomography angiography findings in patients affected by giant cell arteritis, with and without ocular involvement: a pilot study.

Purpose: We evaluated the clinical features and retinal and disk perfusion characteristics by using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in a subset of giant cell arteritis (GCA) patients who manifested anterior ischemic optic neuropathy (AION), in a subset of GCA patients without ocular involvement, and in a control group composed of healthy controls. Methods: We performed an observational study on the eyes of GCA patients affected by arteritic AION both in acute and chronic phases, unaffected eyes of AION, eyes of GCA patients without ocular involvement, and in a control group of healthy eyes of healthy individuals. All patients underwent a complete ophthalmic examination and an OCT and OCTA of the macula and the disk. Results: The study evaluated 10 eyes of GCA patients with AION (AION group), 8 unaffected eyes of GCA patients with AION in another eye (unaffected eyes of AION group), 16 eyes of GCA patients without ocular involvement (non-ocular group), and 22 eyes of healthy patients (healthy group). The ganglion cell complex (GCC) superior and inferior thicknesses were significantly lower in the AION group compared to the unaffected eyes of the AION group (p = 0.045 and p = 0.034, respectively). All OCTA vascular density parameters of the optic disk analyzed in this study (optic nerve head (ONH) whole, superior, inferior, radial peripapillary capillary plexus (RPCP) whole, superior, inferior, lamina cribrosa (LC) whole, superior, inferior) resulted significantly lower in the AION group compared to the unaffected eyes group (p < 0.05 for all the comparisons). The ONH whole and inferior were statistically higher in the healthy group in comparison to the group of GCA patients without ocular involvement (p = 0.008 and p = 0.006, respectively). The ONH inferior was also statistically higher in the unaffected eyes of the AION group in comparison to the non-ocular group (p = 0.045). Regarding the OCTA macular vessel density parameters, the superficial capillary plexus (SCP), whole and inner, were statistically lower in the AION group compared with the unaffected eyes of the AION group. Conclusion: We found a profound vascular impairment in eyes affected by AION and areas of hypoperfusion in the eyes of patients with GCA without ocular involvement, good BCVA, and no clinically significant features. We hypothesized that these areas of lower vessel density might represent areas of subclinical hypoperfusion that cannot be detected ophthalmoscopically.

EN FACE OPTICAL COHERENCE TOMOGRAPHY MORPHOLOGY OF MACULAR PUCKER CORRELATES WITH METAMORPHOPSIA: Possible Role of the Henle Fiber Layer.

PURPOSE: To describe macular pucker contraction patterns with en face optical coherence tomography (OCT), to provide a correlation with metamorphopsia scores, and to discuss the protective role of the Henle fiber layer (HFL) against tangential traction. METHODS: Retrospective, institutional, observational, and consecutive case series. Clinical charts, M-charts scores, and structural and en face OCT imaging of patients diagnosed with macular pucker were reviewed. RESULTS: A 120 eyes of 114 consecutive patients diagnosed with macular pucker were included. En face OCT patterns of macular pucker contraction were foveal in 51 of 120 eyes (42.5%) and extrafoveal in 69 of 120 eyes (57.5%). Foveal macular puckers had regular, a concentric, circle morphology in the HFL (46/51 eyes, 90.2%), whereas extrafoveal membranes had irregular, distorted, circular HFL morphology (62/69 eyes, 89.8%; P < 0.001). Foveal contraction morphology and regular HFL pattern, as well as extrafoveal contraction morphology and an irregular HFL pattern, highly correlated one with another (P < 0.001 in both cases). Foveal macular puckers with regular HFL patterns had significantly less vertical and horizontal M-charts scores as compared with extrafoveal membranes with irregular HFL (P < 0.001 in both cases). Ellipsoid zone and external limiting membrane defects were rare in the parafoveal region (5/120 eyes, 4.2%). Visual acuity did not correlate with metamorphopsia scores (P = 0.903). CONCLUSION: En face OCT imaging identifies macular pucker contraction patterns that correlate with metamorphopsia scores and that can be used alongside the current structural OCT staging system to guide clinicians in the surgical decision-making process.

Utility values and electronic device use in low-vision people attending rehabilitation services: Data from a nation-wide registry in Italy.

PURPOSE: To estimate utility values associated with visual loss using EuroQol (EQ-5D) questionnaire, the impact of low-vision (LV) device use on utilities and the contribution of Instrumental Activities of Daily Living (IADL) score in patients attending vision rehabilitation (VR) services enrolled in the Italian Device & Aids Register (D.A.Re). METHODS: This is a multicenter, prospective, cross-sectional study. D.A.Re. collects general and clinical information, vision-specific variables, use of electronic devices and quality of life questionnaires. RESULTS: A total of 442 patients (75.0±16.6 years, 275 female) were included, 88 (19.9%) used specialised electronic LV devices, and 116 (26.2%) used smartphones and tablets. Users of smartphones and tablets were younger than non-users (67.5 vs. 77.6 years, p<0.001), but overall, their age ranged between 20 and 93. Stronger associations were found between vision-specific variables and IADL score compared to EQ-5D score. In multivariable age-adjusted models, the utility value of using smartphones and tablets on EQ-5D score was 0.12 (p<0.01), slightly larger than that of 1.0 logMAR difference (-0.09, p<0.01) or visual field damage within 10° of fixation (-0.10, p<0.01). Use of portable low-vision electronic devices and being employed or student (vs. retired) was also associated with better utility values (0.12 and 0.15, respectively, p<0.05). CONCLUSIONS: Visual loss is associated with loss of utilities in Italian patients attending VR services, whereas special-purpose electronic aids, and smartphone and tablet use are associated with better utility values. We found that IADL may be more sensitive to visual loss than EQ-5D and could be a valid health-related quality of life outcome in trials on VR.

Multimodal phenotyping of foveal hypoplasia in albinism and albino-like conditions: a pediatric case series with adaptive optics insights.

Aim of the present study is to evaluate the relationship between genetic and phenotypic data in a series of patients affected by grade I and II of foveal hypoplasia with stable fixation and good visual acuity using multimodal imaging techniques. All patients underwent complete clinical and instrumental assessment including structural Optical Coherence Tomography (OCT), OCT Angiography and Adaptive Optics (AO) imaging. Central macular thickness (CMT), inner nuclear layer (INL), vessel density in superficial capillary plexus were the main variables evaluated with OCT technology. Cone density, cone spacing, cone regularity, cone dispersion and angular density were the parameters evaluated with AO. Genetic evaluation and trio exome sequencing were performed in all affected individuals. Eight patients (3 males and 5 females) with a mean age of 12.62 years (range 8-18) were enrolled. The mean best corrected visual acuity (BCVA) was 0.18 ± 0.13 logMAR, mean CMT was 291.9 ± 16.6 µm and INL was 26.2 ± 4.6 µm. The absence of a foveal avascular zone (FAZ) was documented by examination of OCT-A in seven patients in the superficial capillary plexus. However, there was a partial FAZ in the deep plexus in patients P5 and P8. Of note, all the patients presented with major retinal vessels clearly crossing the foveal center. All individuals exhibited a grade I or II of foveal hypoplasia. In 5 patients molecular analyses showed an extremely mild form of albinism caused by compound heterozygosity of a TYR pathogenic variant and the hypomorphic p.[Ser192Tyr;Arg402Gln] haplotype. One patient had Waardenburg syndrome type 2A caused by a de novo variant in MITF. Two patients had inconclusive molecular analyses. All the patients displayed abnormalities on OCT-A. Photoreceptor count did not differ from normal subjects according to the current literature, but qualitative analysis of AO imaging showed distinctive features likely related to an abnormal pigment distribution in this subset of individuals. In patients with foveal hypoplasia, genetic and multimodal imaging data, including AO findings, can help understand the physiopathology of the foveal hypoplasia phenotype. This study confirms that cone density and visual function can both be preserved despite the absence of a pit.

Myopic Macular Hole and Detachment after Gene Therapy in Atypical RPE65 Retinal Dystrophy: A Case Report.

PURPOSE: To report a case of macular hole and detachment occurring after the subretinal injection of Voretigene Neparvovec (VN) in a patient affected by atypical RPE65 retinal dystrophy with high myopia and its successful surgical management. CASE DESCRIPTION: We report a case of a 70-year-old man treated with VN in both eyes. The best corrected visual acuity (BCVA) was 0.7 LogMar in the right eye (RE) and 0.92 LogMar in the left eye (LE). Axial length was 29.60 mm in the RE and 30.28 mm in the LE. Both eyes were pseudophakic. In both eyes, fundus examination revealed high myopia, posterior staphyloma, and extended retinal atrophy areas at the posterior pole, circumscribing a central island of surviving retina. Both eyes were treated with VN subretinal injection, but a full-thickness macular hole and retinal detachment occurred in the LE three weeks after surgery. The patient underwent 23-gauge vitrectomy with internal limiting membrane (ILM) peeling and the inverted flap technique with sulfur hexafluoride (SF6) 20% tamponade. Postoperative follow-up showed that the macular hole was closed and the BCVA was maintained. CONCLUSIONS: Our experience suggests that patients with atypical RPE65 retinal dystrophy and high myopia undergoing VN subretinal injection require careful management to minimize the risk of macular hole and detachment occurrence and promptly detect and address these potential complications.

Role of Vitreous Detachment in Epiretinal Membrane Peeling: A Multimodal Imaging and Microperimetry Study.

Background: To investigate anatomical and functional changes of the macula caused by epiretinal membrane (ERM) peeling procedures in patients with or without posterior vitreous detachment (PVD). Methods: This is a multicentric prospective observational study on thirty-seven (37) patients affected by symptomatic ERM who underwent 25-gauge pars plana vitrectomy (PPV), induction of a PVD (as needed) and peeling of both the internal limiting membrane (ILM) and ERM. Optical coherence tomography-angiography (OCT-A) (RS 3000, Nidek, Japan) and microperimetry (MP-3, Nidek, Japan) were performed; central retinal thickness (CRT), foveal avascular zone (FAZ) area and perimeter, vessel density and perfusion density, retinal sensitivity and fixation stability (as a total mean retinal sensitivity (MRS), and MRS in the ellipse area and bivariate contour ellipse area (BCEA)) were recorded at baseline and up to postoperative month 3. Results: Eyes were classified as having complete PVD (51.4%) or incomplete PVD (48.6%). At baseline, patients with incomplete PVD had worse best-corrected distance visual acuity (BCDVA), total MRS, MRS in the ellipse area and BCEA, and higher CRT than patients with complete PVD. At month 3, the differences in BCDVA between the two groups remained statistically significant, with patients with incomplete PVD having worse results (difference: 0.199 logMAR, p < 0.001). The difference in the MRS in the ellipse area was statistically significant at month 3 (-3.378 Db, p = 0.035), with greater improvement in patients with complete PVD. Conclusions: Our study shows that patients with incomplete PVD have worse conditions at baseline than patients with complete PVD, and the differences in visual acuity and retinal sensitivity were maintained postoperatively.

Atypic Retinitis Pigmentosa Clinical Features Associated with a Peculiar CRX Gene Mutation in Italian Patients.

Purpose: To describe an atypical phenotypic pattern of late-onset retinitis pigmentosa (RP) due to the same specific c.425A>G (p.Tyr142Cys) heterozygous mutation in the cone-rod homeobox gene (CRX gene) in two unrelated Italian patients. Case 1: A 67-year-old woman (P.P.) was incidentally diagnosed with sector RP at the age of 50. The patient was initially asymptomatic and did not have any family history of retinal dystrophy. Fundus examination showed the presence of typical retinal pigmentary deposits with a peculiar pericentral/sector distribution. Genomic sequencing disclosed the missense mutation c.425A>G (p.Tyr142Cys) in the CRX gene. During the follow-up period of 7 years, the patient maintained good visual acuity and complained only of mild symptoms. Case 2: A 76-year-old man (P.E.) presented with nyctalopia and visual field constriction since the age of 50. Fundus examination showed the presence of retinal pigment deposits with a concentric pericentral and perimacular pattern. A full-field electroretinogram (ffERG) showed extinguished scotopic responses and reduced abnormal photopic and flicker cone responses. Genomic sequencing identified the same missense mutation, c.425A>G (p.Tyr142Cys), in the CRX gene. Similarly to the first case, during the whole follow-up of 7 years, the visual acuity remained stable, as did the visual field and the patient's symptoms. Conclusions: We report the first cases of late-onset retinitis pigmentosa related to a specific heterozygous CRX gene mutation in exon 4. We also report two atypical phenotypic RP patterns related to mutations in the CRX gene.

Halo sign on temporal artery ultrasound versus temporal artery biopsy for giant cell arteritis.

BACKGROUND: Giant cell arteritis (GCA) is a systemic, inflammatory vasculitis primarily affecting people over the age of 50 years. GCA is treated as a medical emergency due to the potential for sudden, irreversible visual loss. Temporal artery biopsy (TAB) is one of the five criteria of the American College of Rheumatology (ACR) 1990 classification, which is used to aid the diagnosis of GCA. TAB is an invasive test, and it can be slow to obtain a result due to delays in performing the procedure and the time taken for histopathologic assessment. Temporal artery ultrasonography (US) has been demonstrated to show findings in people with GCA such as the halo sign (a hypoechoic circumferential wall thickening due to oedema), stenosis or occlusion that can help to confirm a diagnosis more swiftly and less invasively, but requiring more subjective interpretation. This review will help to determine the role of these investigations in clinical practice. OBJECTIVES: To evaluate the sensitivity and specificity of the halo sign on temporal artery US, using the ACR 1990 classification as a reference standard, to investigate whether US could be used as triage for TAB. To compare the accuracy of US with TAB in the subset of paired studies that have obtained both tests on the same patients, to investigate whether it could replace TAB as one of the criteria in the ACR 1990 classification. SEARCH METHODS: We used standard Cochrane search methods for diagnostic accuracy. The date of the search was 13 September 2022. SELECTION CRITERIA: We included all participants with clinically suspected GCA who were investigated for the presence of the halo sign on temporal artery US, using the ACR 1990 criteria as a reference standard. We included studies with participants with a prior diagnosis of polymyalgia rheumatica. We excluded studies if participants had had two or more weeks of steroid treatment prior to the investigations. We also included any comparative test accuracy studies of the halo sign on temporal artery US versus TAB, with use of the 1990 ACR diagnostic criteria as a reference standard. Although we have chosen to use this classification for the purpose of the meta-analysis, we accept that it incorporates unavoidable incorporation bias, as TAB is itself one of the five criteria. This increases the specificity of TAB, making it difficult to compare with US. We excluded case-control studies, as they overestimate accuracy, as well as case series in which all participants had a prior diagnosis of GCA, as they can only address sensitivity and not specificity. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion in the review. They extracted data using a standardised data collection form and employed the QUADAS-2 tool to assess methodological quality. As not enough studies reported data at our prespecified halo threshold of 0.3 mm, we fitted hierarchical summary receiver operating characteristic (ROC) models to estimate US sensitivity and also to compare US with TAB. We graded the certainty of the evidence using the GRADE approach. MAIN RESULTS: Temporal artery ultrasound was investigated in 15 studies (617 participants with GCA out of 1479, 41.7%), with sample sizes ranging from 20 to 381 participants (median 69). There was wide variation in sensitivity with a median value of 0.78 (interquartile range (IQR) 0.45 to 0.83; range 0.03 to 1.00), while specificity was fair to good in most studies with a median value of 0.91 (IQR 0.78 to 1.00; range 0.40 to 1.00) and four studies with a specificity of 1.00. The hierarchical summary receiver operating characteristic (HSROC) estimate of sensitivity (95% confidence interval (CI)) at the high specificity of 0.95 was 0.51 (0.21 to 0.81), and 0.84 (0.58 to 0.95) at 0.80 specificity. We considered the evidence on sensitivity and specificity as of very low certainty due to risk of bias (-1), imprecision (-1), and inconsistency (-1). Only four studies reported data at a halo cut-off > 0.3 mm, finding the following sensitivities and specificities (95% CI): 0.80 (0.56 to 0.94) and 0.94 (0.81 to 0.99) in 55 participants; 0.10 (0.00 to 0.45) and 1.00 (0.84 to 1.00) in 31 participants; 0.73 (0.54 to 0.88) and 1.00 (0.93 to 1.00) in 82 participants; 0.83 (0.63 to 0.95) and 0.72 (0.64 to 0.79) in 182 participants. Data on a direct comparison of temporal artery US with biopsy were obtained from 11 studies (808 participants; 460 with GCA, 56.9%). The sensitivity of US ranged between 0.03 and 1.00 with a median of 0.75, while that of TAB ranged between 0.33 and 0.92 with a median of 0.73. The specificity was 1.00 in four studies for US and in seven for TAB. At high specificity (0.95), the sensitivity of US and TAB were 0.50 (95% CI 0.24 to 0.76) versus 0.80 (95% CI 0.57 to 0.93), respectively, and at low specificity (0.80) they were 0.73 (95% CI 0.49 to 0.88) versus 0.92 (95% CI 0.69 to 0.98). We considered the comparative evidence on the sensitivity of US versus TAB to be of very low certainty because specificity was overestimated for TAB since it is one of the criteria used in the reference standard (-1), together with downgrade due to risk of bias (-1), imprecision (-1), and inconsistency (-1) for both sensitivity and specificity. AUTHORS' CONCLUSIONS: There is limited published evidence on the accuracy of temporal artery US for detecting GCA. Ultrasound seems to be moderately sensitive when the specificity is good, but data were heterogeneous across studies and either did not use the same halo thickness threshold or did not report it. We can draw no conclusions from accuracy studies on whether US can replace TAB for diagnosing GCA given the very low certainty of the evidence. Future research could consider using the 2016 revision of the ACR criteria as a reference standard, which will limit incorporation bias of TAB into the reference standard.

Diabetic Retinopathy and Quality of Life: A Systematic Review and Meta-Analysis.

Importance: The association between diabetic retinopathy (DR) and quality of life (QoL) has not been thoroughly investigated. Objective: To investigate the association between DR and both vision-related QoL (VRQoL) and general health-related QoL (HRQoL). Data Sources: MEDLINE, EBSCO, Embase, and Web of Science were searched from their inception to April 2022. Study Selection: Studies included adults with DR and a measure of QoL. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Two assumption-free meta-analyses were conducted. Analysis 1 included studies with participants without DR as the referent group to which QoL scores of participants with DR, grouped according to DR severity, were compared. Analysis 2 included all studies with participants with DR and a measure of QoL. QoL scores were pooled within categories of DR severity, and comparisons were made between these categories. Main Outcome and Measures: QoL measured using HRQoL and VRQoL scales. Results: A total of 93 articles were included: 79 in the meta-analyses and 14 in the narrative results. VRQoL was recorded in 54 studies, HRQoL in 26, and both in 13 studies. The most commonly used scales were the National Eye Institute 25-item Visual Function Questionnaire (VFQ-25) (n = 49) for VRQoL and the Short Form (SF) Health Survey (n = 18) for HRQoL. Thirty-five studies reported VFQ-25 composite scores. Analysis 1 consisted of 8 studies including 1138 participants with DR and 347 participants without DR. Compared with participants without DR, the composite VFQ-25 score was 3.8 (95% CI, 1.0-6.7) points lower in those with non-vision-threatening DR (NVTDR), 12.5 (95% CI, 8.5-16.5) lower in those with any DR, and 25.1 (95% CI, 22.8-27.2) lower in VTDR (P < .001 for trend). Analysis 2 consisted of 35 studies including 6351 participants with DR. The pooled mean VFQ-25 composite score was 91.8 (95% CI, 91.0-92.7) for participants with NVTDR, 77.6 (95% CI, 76.9-78.3) for any DR, and 73.2 (95% CI, 72.6-73.7) for VTDR (P < .001 for trend). HRQoL scores had weak or no associations with NVTDR and strong associations with VTDR. Conclusions and Relevance: This study found that VRQoL declined with the presence and severity of DR. Interventions to reduce progression of DR at both early and more advanced stages could improve VRQoL.

Use of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) questionnaires for clinical decision-making and psychological referral in ophthalmic care: a multicentre observational study.

OBJECTIVES: The aim of this study was to evaluate the influence of anxiety and depression on clinician decision-making in patients suffering from chronic eye disease in ophthalmological clinical practice. DESIGN AND SETTING: This multicentre observational study, in collaboration with the WHO, included ophthalmologists and their patients affected by chronic eye disease. States of anxiety and depression were screened with specific questionnaires, the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), self-administered by patients before the visit. In the present analysis, we report data from three major eye care centres in Italy between 2021 and 2022. PRIMARY AND SECONDARY OUTCOMES: To assess self-reported changes in ophthalmologists' clinical approach (communication style and their clinical-therapeutic strategies) and decisions after knowing questionnaire scores (primary aim), and to analyse the PHQ-9 and GAD-7 scores in patients with chronic eye diseases (secondary aim). RESULTS: 41 ophthalmologists and 359 patients were included. The results from PHQ-9 and GAD-7 scores showed critical depression and anxiety status scores (PHQ-9 ≥5 and GAD-7 ≥10) in 258 patients. In 74% of cases, no actions were taken by the ophthalmologists based on these scores; in 26% of cases, they changed their clinical approach; and in 14% of cases, they referred the patients for psychological/psychiatric evaluation. CONCLUSIONS: States of anxiety and depression affect many patients with chronic eye conditions and need to be detected and managed early to improve patients' well-being. Providing ophthalmologists with knowledge of their patients' psychological conditions can change the clinical management and attitude towards referral for a psychological evaluation. Further studies are needed to expand our knowledge of how to raise awareness among ophthalmologists regarding multimorbidity of patients suffering from chronic eye diseases in order to achieve better clinical outcomes.

Hypotony Failure Criteria in Glaucoma Surgical Studies and Their Influence on Surgery Success.

PURPOSE: Review hypotony failure criteria used in glaucoma surgical outcome studies and evaluate their impact on success rates. DESIGN: Systematic literature review and application of hypotony failure criteria to 2 retrospective cohorts. PARTICIPANTS: A total of 934 eyes and 1765 eyes undergoing trabeculectomy and deep sclerectomy (DS) with a median follow-up of 41.4 and 45.4 months, respectively. METHODS: Literature-based hypotony failure criteria were applied to patient cohorts. Intraocular pressure (IOP)-related success was defined as follows: (A) IOP ≤ 21 mmHg with ≥ 20% IOP reduction; (B) IOP ≤ 18 mmHg with ≥ 20% reduction; (C) IOP ≤ 15 mmHg with ≥ 25% reduction; and (D) IOP ≤ 12 mmHg with ≥ 30% reduction. Failure was defined as IOP exceeding these criteria in 2 consecutive visits > 3 months after surgery, loss of light perception, additional IOP-lowering surgery, or hypotony. Cox regression estimated failure risk for different hypotony criteria, using no hypotony as a reference. Analyses were conducted for each criterion and hypotony type (i.e., numerical [IOP threshold], clinical [clinical manifestations], and mixed [combination of numerical or clinical criteria]). MAIN OUTCOME MEASURES: Hazard ratio (HR) for failure risk. RESULTS: Of 2503 studies found, 278 were eligible, with 99 studies (35.6%) lacking hypotony failure criteria. Numerical hypotony was predominant (157 studies [56.5%]). Few studies used clinical hypotony (3 isolated [1.1%]; 19 combined with low IOP [6.8%]). Forty-nine different criteria were found, with IOP < 6 mmHg, IOP < 6 mmHg on ≥ 2 consecutive visits after 3 months, and IOP < 5 mmHg being the most common (41 [14.7%], 38 [13.7%], and 13 [4.7%] studies, respectively). In both cohorts, numerical hypotony posed the highest risk of failure (HR, 1.51-1.21 for criteria A to D; P < 0.001), followed by mixed hypotony (HR, 1.41-1.20 for criteria A to D; P < 0.001), and clinical hypotony (HR, 1.12-1.04; P < 0.001). Failure risk varied greatly with various hypotony definitions, with the HR ranging from 1.02 to 10.79 for trabeculectomy and 1.00 to 8.36 for DS. CONCLUSIONS: Hypotony failure criteria are highly heterogenous in the glaucoma literature, with few studies focusing on clinical manifestations. Numerical hypotony yields higher failure rates than clinical hypotony and can underestimate glaucoma surgery success rates. Standardizing failure criteria with an emphasis on clinically relevant hypotony manifestations is needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Vitreomacular interface abnormalities in the Ghanaian African.

BACKGROUND/OBJECTIVE: Describe vitreomacular interface abnormalities (VMIA) using spectral-domain optical coherence tomography (SD-OCT), and correlations with age-related macular degeneration (AMD) grade in Ghanaian Africans. SUBJECTS/METHODS: Prospective, cross-sectional study of adults aged ≥50 years recruited in Ghana AMD Study. Participant demographics, medical histories, ophthalmic examination, digital colour fundus photography (CFP) were obtained. High-resolution five-line raster OCT, Macular Cube 512 × 128 scans, and additional line scans in areas of clinical abnormality, were acquired. SD-OCT VMI features classified by International Vitreomacular Traction Study Group system and relationships to AMD grade were evaluated. OUTCOMES: VMIA prevalence, posterior vitreous detachment (PVD), vitreomacular adhesions (VMA), vitreomacular traction (VMT), epiretinal membranes (ERM), correlations with AMD grade. RESULTS: The full Ghana AMD cohort included 718 participants; 624 participants (1248 eyes) aged ≥50 years (range = 50-101, mean = 68.8), 68.9% female were included in this analysis. CFP with OCT scans were available for 776 eyes (397 participants); 707 (91.1%) had gradable CFP and OCT scans for both AMD and VMI grading forming the dataset for this report. PVD was absent in 504 (71.3%); partial and complete PVD occurred in 16.7% and 12.0% respectively. PVD did not increase with age (p = 0.720). VMIA without traction and macular holes were observed in 12.2% of eyes; 87.8% had no abnormalities. VMIA was not significantly correlated with AMD grade (p = 0.819). CONCLUSIONS: This provides the first assessment of VMIA in Ghanaian Africans. VMIA are common in Africans; PVD may be less common than in Caucasians. There was no significant association of AMD grade with VMIA.

Impact of Vision Impairment and Ocular Morbidity and Their Treatment on Quality of Life in Children: A Systematic Review.

TOPIC: This review summarizes existing evidence of the impact of vision impairment and ocular morbidity and their treatment on children's quality of life (QoL). CLINICAL RELEVANCE: Myopia and strabismus are associated with reduced QoL among children. Surgical treatment of strabismus significantly improves affected children's QoL. METHODS: We conducted a systematic review and meta-analysis by screening articles in any language in 9 databases published from inception through August 22, 2022, addressing the impact of vision impairment, ocular morbidity, and their treatment on QoL in children. We reported pooled standardized mean differences (SMDs) using random-effects meta-analysis models. Quality appraisal was performed using Joanna Briggs Institute and National Institutes of Health tools. This study was registered with the International Prospective Register of Systematic Reviews (identifier, CRD42021233323). RESULTS: Our search identified 29 118 articles, 44 studies (0.15%) of which were included for analysis that included 32 318 participants from 14 countries between 2005 and 2022. Seventeen observational and 4 interventional studies concerned vision impairment, whereas 10 observational and 13 interventional studies described strabismus and other ocular morbidities. Twenty-one studies were included in the meta-analysis. The QoL scores did not differ between children with and without vision impairment (SMD, -1.04; 95% confidence interval [CI], -2.11 to 0.03; P = 0.06; 9 studies). Myopic children demonstrated significantly lower QoL scores than those with normal vision (SMD, -0.60; 95% CI, -1.09 to -0.11; P = 0.02; 7 studies). Children with strabismus showed a significantly lower QoL score compared with those without (SMD, -1.19; 95% CI, -1.66 to -0.73; P < 0.001; 7 studies). Strabismus surgery significantly improved QoL in children (SMD, 1.36; 95% CI, 0.48-2.23; P < 0.001; 7 studies). No randomized controlled trials (RCTs) concerning refractive error and QoL were identified. Among all included studies, 35 (79.5%) were scored as low to moderate quality; the remaining met all quality appraisal tools criteria. DISCUSSION: Reduced QoL was identified in children with myopia and strabismus. Surgical correction of strabismus improves the QoL of affected children, which supports insurance coverage of strabismus surgery. Further studies, especially RCTs, investigating the impact of correction of myopia on QoL are needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

IMAGING RHEGMATOGENOUS RETINAL LESIONS AND PERIPHERAL VITREORETINAL INTERFACE WITH WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: Analyze the peripheral vitreoretinal interface with widefield optical coherence tomography. METHODS: Retrospective chart analysis and widefield optical coherence tomography in 120 consecutive cases of rhegmatogenous pathology. RESULTS: There were 166 lesions in 120 eyes, including 106 horseshoe tears, 22 operculated holes, 30 nonoperculated holes, six giant tears, and two peripheral lamellar defects followed for 6.1 ± 1.2 months. Posterior vitreous detachment was present in all eyes (101/101, 100%) with tears and operculated holes, but only in 5/19 eyes (26.3%) with nonoperculated holes ( P < 0.001). Axial vitreous traction was evident at the anterior edge of horseshoe tears (106/106, 100%), but not the posterior border (18/106, 17%, P < 0.001). Operculated holes located posterior to the vitreous base were free from vitreous traction, displaying a morphology similar to the macular hole. Nonoperculated holes were farther anterior with signs of tangential traction in 23/30 (76.7%) cases. Peripheral vitreoschisis was more often associated with nonoperculated holes (25/30, 83.3%), than horseshoe tears (17/106, 16%; P < 0.001). Horseshoe tears and nonoperculated holes were more often associated with retinal detachment (58/106 [54.7%] and 15/30 [50%], respectively) than operculated holes (5/22, 22.7%), P = 0.023. CONCLUSION: Peripheral vitreoretinal interactions are similar to vitreomaculopathies, with axial and vitreoschisis-related tangential traction playing different roles in different rhegmatogenous pathologies. Peripheral optical coherence tomography improves understanding of pathophysiology and risks of retinal detachment.

Combined or sequential DMEK in cases of cataract and Fuchs endothelial corneal dystrophy-A systematic review and meta-analysis.

To compare the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed after phacoemulsification and intraocular lens (IOL) implantation (sequential DMEK) and DMEK combined with phacoemulsification and IOL implantation (combined DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD) and cataract. Systematic literature review and meta-analysis performed according to the PRISMA guidelines and registered in PROSPERO. Literature searches were conducted in Medline and Scopus. Comparative studies reporting sequential DMEK and combined DMEK in FECD patients were included. The main outcome measure of the study was the corrected distance visual acuity (CDVA) improvement. Secondary outcomes were postoperative endothelial cell density (ECD), rebubbling rate and primary graft failure rate. Bias risk was assessed and a quality appraisal of the body of evidence was completed using the Cochrane Robin-I tool. A total of 667 eyes (5 studies) were included in this review, 292 eyes (43.77%) underwent a combined DMEK, while 375 (56.22%) eyes underwent a sequential DMEK surgery. We found no evidence of a difference between the two groups (mean difference, 95% CI) regarding: (1) CDVA improvement (-0.06; -0.14, 0.03 LogMAR; 3 studies, I2 : 0%; p = 0.86); (2) postoperative ECD (-62; -190, 67 cells/mm2 ; 4 studies, I2 : 67%; p = 0.35); (3) rebubbling (risks ratio: 1.04; 0.59, 1.85; 4 studies, I2 : 48%; p = 0.89); and primary graft failure rate (risks ratio: 0.91; 0.32, 2.57; 3 studies, I2 : 0%; p = 0.86). Of all the 5 non-randomized studies, all (100%) were graded as low quality. The overall quality of the analysed studies was low. Randomized controlled trials are needed to confirm no difference or superiority of one approach in terms of CDVA, endothelial cell count and postoperative complication rate between the two arms.

Antimicrobials and antiseptics: Lowering effect on ocular surface bacterial flora - A systematic review.

Topical antimicrobials and antiseptics are used perioperatively to reduce the ocular surface bacteria flora (OSBF) that are involved in the development of post-operative infectious complications. However, their effectiveness is still a controversial topic. This systematic review, performed according to the PRISMA guidelines and registered in PROSPERO, aims to provide an overview of the efficacy of the agents currently used in peri-cataract surgery and -intravitreal injections (IVI) in lowering the OSBF. Although effective in lowering OSBF, perioperative topical antimicrobials are associated with the risk of resistance development, with no obvious additional benefit compared with topical antisepsis. Conversely, the effectiveness of topical antiseptics before cataract surgery and IVI is strongly supported. Based on the available evidence, perioperative antimicrobials are not recommended, whereas the perioperative use of antiseptics is strongly recommended as prophylactic treatment for lowering the infection due to OSBF. Post-operative antimicrobials may be considered in eyes at higher risk for infection.

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects mainly young adults (two to three times more frequently in women than in men) and causes significant disability after onset. Although it is accepted that immunotherapies for people with MS decrease disease activity, uncertainty regarding their relative safety remains. OBJECTIVES: To compare adverse effects of immunotherapies for people with MS or clinically isolated syndrome (CIS), and to rank these treatments according to their relative risks of adverse effects through network meta-analyses (NMAs). SEARCH METHODS: We searched CENTRAL, PubMed, Embase, two other databases and trials registers up to March 2022, together with reference checking and citation searching to identify additional studies. SELECTION CRITERIA: We included participants 18 years of age or older with a diagnosis of MS or CIS, according to any accepted diagnostic criteria, who were included in randomized controlled trials (RCTs) that examined one or more of the agents used in MS or CIS, and compared them versus placebo or another active agent. We excluded RCTs in which a drug regimen was compared with a different regimen of the same drug without another active agent or placebo as a control arm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for data extraction and pairwise meta-analyses. For NMAs, we used the netmeta suite of commands in R to fit random-effects NMAs assuming a common between-study variance. We used the CINeMA platform to GRADE the certainty of the body of evidence in NMAs. We considered a relative risk (RR) of 1.5 as a non-inferiority safety threshold compared to placebo. We assessed the certainty of evidence for primary outcomes within the NMA according to GRADE, as very low, low, moderate or high. MAIN RESULTS: This NMA included 123 trials with 57,682 participants. Serious adverse events (SAEs) Reporting of SAEs was available from 84 studies including 5696 (11%) events in 51,833 (89.9%) participants out of 57,682 participants in all studies. Based on the absolute frequency of SAEs, our non-inferiority threshold (up to a 50% increased risk) meant that no more than 1 in 18 additional people would have a SAE compared to placebo. Low-certainty evidence suggested that three drugs may decrease SAEs compared to placebo (relative risk [RR], 95% confidence interval [CI]): interferon beta-1a (Avonex) (0.78, 0.66 to 0.94); dimethyl fumarate (0.79, 0.67 to 0.93), and glatiramer acetate (0.84, 0.72 to 0.98). Several drugs met our non-inferiority criterion versus placebo: moderate-certainty evidence for teriflunomide (1.08, 0.88 to 1.31); low-certainty evidence for ocrelizumab (0.85, 0.67 to 1.07), ozanimod (0.88, 0.59 to 1.33), interferon beta-1b (0.94, 0.78 to 1.12), interferon beta-1a (Rebif) (0.96, 0.80 to 1.15), natalizumab (0.97, 0.79 to 1.19), fingolimod (1.05, 0.92 to 1.20) and laquinimod (1.06, 0.83 to 1.34); very low-certainty evidence for daclizumab (0.83, 0.68 to 1.02). Non-inferiority with placebo was not met due to imprecision for the other drugs: low-certainty evidence for cladribine (1.10, 0.79 to 1.52), siponimod (1.20, 0.95 to 1.51), ofatumumab (1.26, 0.88 to 1.79) and rituximab (1.01, 0.67 to 1.52); very low-certainty evidence for immunoglobulins (1.05, 0.33 to 3.32), diroximel fumarate (1.05, 0.23 to 4.69), peg-interferon beta-1a (1.07, 0.66 to 1.74), alemtuzumab (1.16, 0.85 to 1.60), interferons (1.62, 0.21 to 12.72) and azathioprine (3.62, 0.76 to 17.19). Withdrawals due to adverse events Reporting of withdrawals due to AEs was available from 105 studies (85.4%) including 3537 (6.39%) events in 55,320 (95.9%) patients out of 57,682 patients in all studies. Based on the absolute frequency of withdrawals, our non-inferiority threshold (up to a 50% increased risk) meant that no more than 1 in 31 additional people would withdraw compared to placebo. No drug reduced withdrawals due to adverse events when compared with placebo. There was very low-certainty evidence (meaning that estimates are not reliable) that two drugs met our non-inferiority criterion versus placebo, assuming an upper 95% CI RR limit of 1.5: diroximel fumarate (0.38, 0.11 to 1.27) and alemtuzumab (0.63, 0.33 to 1.19). Non-inferiority with placebo was not met due to imprecision for the following drugs: low-certainty evidence for ofatumumab (1.50, 0.87 to 2.59); very low-certainty evidence for methotrexate (0.94, 0.02 to 46.70), corticosteroids (1.05, 0.16 to 7.14), ozanimod (1.06, 0.58 to 1.93), natalizumab (1.20, 0.77 to 1.85), ocrelizumab (1.32, 0.81 to 2.14), dimethyl fumarate (1.34, 0.96 to 1.86), siponimod (1.63, 0.96 to 2.79), rituximab (1.63, 0.53 to 5.00), cladribine (1.80, 0.89 to 3.62), mitoxantrone (2.11, 0.50 to 8.87), interferons (3.47, 0.95 to 12.72), and cyclophosphamide (3.86, 0.45 to 33.50). Eleven drugs may have increased withdrawals due to adverse events compared with placebo: low-certainty evidence for teriflunomide (1.37, 1.01 to 1.85), glatiramer acetate (1.76, 1.36 to 2.26), fingolimod (1.79, 1.40 to 2.28), interferon beta-1a (Rebif) (2.15, 1.58 to 2.93), daclizumab (2.19, 1.31 to 3.65) and interferon beta-1b (2.59, 1.87 to 3.77); very low-certainty evidence for laquinimod (1.42, 1.01 to 2.00), interferon beta-1a (Avonex) (1.54, 1.13 to 2.10), immunoglobulins (1.87, 1.01 to 3.45), peg-interferon beta-1a (3.46, 1.44 to 8.33) and azathioprine (6.95, 2.57 to 18.78); however, very low-certainty evidence is unreliable. Sensitivity analyses including only studies with low attrition bias, drug dose above the group median, or only patients with relapsing remitting MS or CIS, and subgroup analyses by prior disease-modifying treatments did not change these figures. Rankings No drug yielded consistent P scores in the upper quartile of the probability of being better than others for primary and secondary outcomes. AUTHORS' CONCLUSIONS: We found mostly low and very low-certainty evidence that drugs used to treat MS may not increase SAEs, but may increase withdrawals compared with placebo. The results suggest that there is no important difference in the occurrence of SAEs between first- and second-line drugs and between oral, injectable, or infused drugs, compared with placebo. Our review, along with other work in the literature, confirms poor-quality reporting of adverse events from RCTs of interventions. At the least, future studies should follow the CONSORT recommendations about reporting harm-related issues. To address adverse effects, future systematic reviews should also include non-randomized studies.