Superficial and Deep Capillary Plexuses: Potential Biomarkers of Focal Retinal Defects in Eyes Affected by Macular Idiopatic Epiretinal Membranes? A Pilot Study.

Inner macular layers are the most involved in the retinal distortion caused by idiopathic epiretinal membrane (iERM). They represent the anatomical structures in which the superficial (SCP) and deep (DCP) capillary plexus are embedded. We quantified flow signal (FS) in these capillary plexuses using Swept Source OCT angiography to identify possible markers for postoperative outcome. The software ImageJ was used to quantify the FS in a 150 µm radius area around each point analyzed by MAIA microperimeter. In 16 patients with unilateral iERM, focal light sensitivity (FLS) in the para- and perimacular areas was measured to evaluate macular function in 24 points overlapping macular plexuses and compared with normal fellow eyes (FEs). t-Test for independent samples iERM eyes (iERMEs) vs. fellow eyes (FEs) and Pearson correlation coefficient of FS vs. FLS in each point were calculated. A level of p < 0.05 was accepted as statistically significant. As a whole, FLS was significantly higher in FEs vs. ERMEs (p < 0.001); FS in both SCP and DCP was not significantly different between ERMEs and FEs (p = 0.827, p = 0.791). Correlation in focal retinal areas between FLS and FS in ERMEs was significant in SCP (p = 0.002) and not significant in DCP (p = 0.205); in FEs was significant in both SCP (p < 0.001) and DCP (p = 0.022). As previously described, these defective areas were located mainly in sites of distortion of retinal layers; therefore, it can be hypothesized that a focal change in FS, occurring mostly in SCP, could be involved in the onset of the functional defect.

A Novel Autosomal Recessive Variant of the NRL Gene Causing Enhanced S-Cone Syndrome: A Morpho-Functional Analysis of Two Unrelated Pediatric Patients.

Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal degeneration mainly associated with pathogenic variations in the NR2E3 gene. Only a few pathogenic variations in the NRL gene associated with ESCS have been reported to date. Here, we describe the clinical and genetic findings of two unrelated pediatric patients with a novel frameshift homozygous variant in the NRL gene. Fundus examinations showed signs of peripheral degeneration in both patients, more severe in Proband 2, with relative sparing of the macular area. Spectral domain optical coherence tomography (SD-OCT) revealed a significant macular involvement with cysts in Proband 1, and minimal foveal alteration with peripheral retina involvement in Proband 2. Visual acuity was abnormal in both patients, but more severely affected in Proband 1 than Proband 2. The electroretinogram recordings showed reduced scotopic, mixed and single flash cone responses, with a typical supernormal S-cone response, meeting the criteria for a clinical diagnosis of ESCS in both patients. The present report expands the clinical and genetic spectrum of NRL-associated ESCS, and confirms the age-independent variability of phenotypic presentation already described in the NR2E3-associated ESCS.

Genetics of Inherited Retinal Diseases in Understudied Ethnic Groups in Italian Hospitals.

Purpose: Describing the clinical and genetic features of an ethnically heterogeneous group of (inherited retinal diseases) IRD patients from different underrepresented countries, referring to specialized Italian Hospitals, and expanding the epidemiological spectrum of the IRD in understudied populations. Methods: The patients' phenotypes underwent were characterized by exhaustive ophthalmological examinations, including morpho-functional testing. Genetic testing was performed using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and-when necessary-multiplex ligation-dependent probe amplification (MLPA) to better identify the genotype. When possible, segregation analysis was performed in order to confirm unsolved cases. Results: The article reports the results of the phenotypes and genotypes of 123 IRD probands, 69 males and 54 females, mean age 41 (IQR, 54-30) years, disease onset at 13 (IQR, 27.25-5) years. Thirty-three patients out of 123 (26.8%) were Africans (North/Northwest Africa), 21 (17.1%) Asians, 19 (15.4%) Americans (South/Central America) and 50 (40.7%) Europeans (Eastern Europe). Retinitis pigmentosa was the most represented phenotype (56%), followed by cone dystrophy (11%) and Leber congenital amaurosis (7%), while ABCA4 was the most frequently mutated gene (18%), followed by USH2A (9%) and RPGR (5%). About ABCA4 variants found in Stargardt disease, macular and cone dystrophies were predominant in Asian (42%) and European (21%) patients. The most represented inheritance pattern was autosomal recessive, while a higher frequency of homozygous patients versus compound heterozygotes as compared to previous studies on Italian IRD patients was evidenced, reflecting a possible higher frequency of inbreeding marriages. Conclusion: Though limited by the relatively low number of patients, the present paper paints a picture of the clinical and genetic features of IRD patients from understudied ethnic groups referred to Italian specialized hospitals and extended the epidemiological studies on underrepresented world regional areas.

Dexamethasone Intravitreal Implant (Ozurdex) in Paediatric Patients with Non-infectious Intermediate Uveitis and Related Cystoid Macular Oedema: Evaluation of Macular Morphology and Function with Six-month Follow-up; a Deeper Role of MfERG?

PURPOSE: To evaluate the efficacy of Ozurdex implant by analyzing macular morphology and function in pediatric uveitis and related cystoid macular edema (CMO). METHODS: Main outcomes were visual acuity, mfERG and photopic ERG response, and central macular thickness. Mean values recorded at each time-point were compared to baseline and correlations between functional and anatomical parameters were evaluated. RESULTS: Resolution of intraocular inflammation and CMO was achieved in all eyes 1 month after implant without procedure or drug-related complications. Mean visual acuity and mfERG amplitude improved showing a statistically significant difference to baseline values for the first 4 months. Mean central macular thickness showed a statistically significant reduction for all follow-up time. Photopic ERG did not vary significantly. Statistically significant correlation was found between trends of visual acuity, central macular thickness, and mfERG responses. CONCLUSION: Correlation found between macular morphology and function confirms the efficacy of Ozurdex in pediatric uveitis.

Blue Cone Monochromatism with Foveal Hypoplasia Caused by the Concomitant Effect of Variants in OPN1LW/OPN1MW and GPR143 Genes.

Blue cone monochromatism (BCM) is an X-linked recessive cone dysfunction disorder caused by mutations in the OPN1LW/OPN1MW gene cluster, encoding long (L)- and middle (M)-wavelength-sensitive cone opsins. Here, we report on the unusual clinical presentation of BCM caused by a novel mutation in the OPN1LW gene in a young man. We describe in detail the phenotype of the proband, and the subclinical morpho-functional anomalies shown by his carrier mother. At a clinical level, the extensive functional evaluation demonstrated in the proband the M/L cone affection and the sparing of S-cone function, distinctive findings of BCM. Interestingly, spectral-domain optical coherence tomography showed the presence of foveal hypoplasia with focal irregularities of the ellipsoid layer in the foveal area, reported to be associated with some cases of cone-rod dystrophy and achromatopsia. At a molecular level, we identified the novel mutation c.427T > C p.(Ser143Pro) in the OPN1LW gene and the common missense mutation c.607T > C (p.Cys203Arg) in the OPN1MW gene. In addition, we discovered the c.768-2_769delAGTT splicing variant in the GPR143 gene. To our knowledge, this is the first case of foveal hypoplasia in a BCM patient and of mild clinical affection in a female carrier caused by the concomitant effect of variants in OPN1LW/OPN1MW and GPR143 genes, thus as the result of the simultaneous action of two independent genetic defects.

Microperimetric retinal changes in myopic choroidal neovascularization treated with intravitreal ranibizumab.

PURPOSE: The purpose of this study was to report functional and morphologic retinal changes after intravitreal injections of 0.5 mg ranibizumab in patients with myopic neovascular membrane (choroidal neovascularization). METHODS: This is a case review of 11 consecutive patients with myopic choroidal neovascularization who received intravitreal injections of ranibizumab at monthly intervals. Serial changes in best-corrected visual acuity, optical coherence tomography, fluorescein angiography, and microperimetry (Nidek MP1, Nidek, Padova, Italy) are presented. RESULTS: Mean baseline best-corrected visual acuity was 59.82 + or - 17.50 Early Treatment Diabetic Retinopathy Study letters. After a follow-up of 36 weeks, mean visual acuity improved to 66.72 + or - 17.3 with a mean change of 6.91 letters. Mean baseline retinal sensitivity was 6.02 + or - 1.9 dB. After 36 weeks, mean sensitivity improved to 8.3 + or - 2.4 dB with a mean change of 2.3 dB. The fixation stability improved from 45.5% to 72.7%. All patients also had complete resolution of subretinal fluid, mean optical coherence tomography central retinal thickness was reduced from 244.64 + or - 39.3 microm to 191.36 + or - 27.3 microm at 36 weeks, and fluorescein angiography at 36 weeks showed absence of leakage in all patients. CONCLUSION: Intravitreal ranibizumab injections seemed to positively influence retinal functional status in patients with myopic choroidal neovascularization.

Fellow eye findings of highly myopic subjects operated for retinal detachment associated with a macular hole.

PURPOSE: To identity anatomic risk factors involved in the onset of retinal complications causing decrease of visual acuity (VA) in the fellow eyes of highly myopic patients operated for retinal detachment with macular hole (RDMH). DESIGN: Cohort study. PARTICIPANTS: Ninety-eight patients (mean age, 51.5+/-8.0 years) with bilateral high myopia (mean myopia of the fellow eye, 20.4+/-5.5 diopters) affected by RDMH in the other eye at baseline. METHODS: Evaluation of the anatomic features at baseline and during 84+/-2.7 months of follow-up by biomicroscopic examination, indirect binocular ophthalmoscopy, B-scan ultrasonography, and optical coherence tomography. MAIN OUTCOME MEASURES: Detection of anatomic features associated with onset of retinal complications causing decrease of VA during the follow-up period. RESULTS: The fellow eyes were divided into 2 groups according to the clinical features of the RDMH eyes: Group 1, presence of posterior vitreous detachment (PVD); and Group 2, presence of posterior vitreous schisis (PVS). At baseline, the incidence of PVD in group 1 was 31 of 47 eyes (65.9%) and the incidence of PVS in Group 2 was 42 of 51 eyes (82.3%). At the end of follow-up, group 1 eyes had a lower incidence of retinal complications causing visual decrease than group 2 eyes (group 1, 2/47 eyes; group 2, 9/51 eyes). CONCLUSIONS: Fellow eyes of RDMH cases with higher degree of myopia and peculiar vitreoretinal features including PVS, posterior epiretinal membrane, severe posterior staphyloma, and chorioretinal atrophy are more likely to develop retinal complications causing decrease of VA.

Assessment of macular function by focal electroretinogram and pattern electroretinogram before and after epimacular membrane surgery.

PURPOSE: To evaluate macular function before and after surgical peeling of idiopathic epimacular membrane (EMM). METHODS: Logarithm of the minimal angle of resolution visual acuity and results of focal (central 9 x 9 degrees) electroretinogram (fERG), pattern electroretinogram (pERG), and optical coherence tomography (OCT) assessment of macular volume were evaluated for 22 eyes of 22 patients (mean age +/- SD, 63.20 +/- 10.0 years) with EMM preoperatively (baseline) and 6 months after surgical peeling. Preoperative visual acuity and fERG and pERG amplitudes observed in EMM eyes were compared with those in 15 age-matched control eyes. RESULTS: In the preoperative evaluation, EMM eyes had a significant (P < 0.01; one-way analysis of variance) reduction in visual acuity and fERG and pERG amplitudes and an increase in OCT macular volume when compared with controls. In EMM eyes, the decrease in visual acuity was significantly correlated (P < 0.01, Pearson test) to the reduction in fERG and pERG amplitudes. At the postoperative evaluation, EMM eyes had a correlated significant (P < 0.01) increase in visual acuity, fERG amplitude, and pERG amplitude with respect to the preoperative values. All EMM eyes had a significant (P <0.01) reduction in macular volume, and retinal microanatomy was restored to normal conditions. CONCLUSION: In EMM eyes, the decrease in visual acuity is related to dysfunction of both preganglionic (abnormal fERG) and ganglionic (abnormal pERG) macular elements. Surgical removal of EMM may induce improvement of the function of both outer and innermost macular retinal layers, leading to a related increase in visual acuity.

Posterior vitreous detachment and retinal detachment after cataract surgery.

OBJECTIVE: To evaluate possible changes of vitreous status in emmetropic eyes after uneventful phacoemulsification surgery, and possible related complications such as the onset of retinal detachment (RD). DESIGN: Retrospective case series. PARTICIPANTS: Four hundred fifty-three emmetropic eyes from 453 patients (mean age, 62.03+/-5.57 years) subjected to uneventful phacoemulsification with intraocular lens implantation in the capsular bag were considered in the study. They had a refractive error within +/-0.5 diopters (mean, -0.21+/-0.08). Eyes with peripheral retinal lattice degeneration were included only if asymptomatic and only if the degeneration involved one retinal quadrant. After cataract surgery, the 453 eyes were evaluated preoperatively at days 1, 15, and 30 and months 3, 6, 12, 18, 24, 36, 48, and 60. The whole period of follow-up was 5 years. METHODS: Evaluation of vitreous status by biomicroscopic examination, indirect binocular ophthalmoscopy, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Postoperative onset of posterior vitreous detachment (PVD) and RD. RESULTS: After cataract surgery, a PVD occurred in 107 of 141 (75.88%) eyes without preoperative PVD or lattice degeneration. Posterior vitreous detachment occurred in 41 of 47 eyes (87.23%) with preoperative lattice degeneration and no PVD. Eyes with preoperative lattice degeneration and postoperative PVD showed a higher incidence of RD after cataract surgery (21.27%) than eyes without preoperative PVD or lattice degeneration (0.70%). In all patients with lattice degeneration, RD originated from horseshoe retinal tears on lattice areas located on the superior quadrants. No correlation was observed between the development of RD and age. CONCLUSIONS: Our results suggest that the onset of postoperative PVD should be considered an important risk factor for the development of RD after cataract surgery, particularly in eyes with lattice areas.

Prevalence of asymptomatic macular holes in highly myopic eyes.

OBJECTIVE: To evaluate the presence of macular holes (MHs) in very highly myopic eyes in the absence of visual symptoms. DESIGN: Retrospective case series. PARTICIPANTS: Three hundred eighty-three eyes from 383 patients (mean age, 51.70+/-12.73 years) affected by very high myopia (between -14 and -32 diopters [D]), with no visual disturbance such as metamorphopsia and with visual acuity (VA) of >0.2 logarithm of the minimum angle of resolution, were considered in the study. They were evaluated at baseline and every 6 months during a mean total period of 30.2+/-0.5 months (range, 28.3-32.1). METHODS: Evaluation of macular morphology by optical coherence tomography (OCT). MAIN OUTCOME MEASURES: Changes in OCT macular morphology ascribed to the presence of an MH. RESULTS: Macular holes were detected by OCT in 24 of 383 (6.26%) myopic eyes. These MHs were defined as asymptomatic (AMHs). The presence of AMHs was more prevalent (although not significantly when compared with the overall study population) in myopic patients younger than 50 years and with concomitant myopia of >-20 D. Posterior vitreous schisis was the most frequent vitreous modification associated with AMH (18/24 eyes [75.0%]). During follow-up, a decrease in VA was observed in 5 of 24 (20.8%) AMH eyes due to the enlargement of the lesion or to posterior retinal detachment, leading to the development of a symptomatic MH. Greater degree of myopia and younger age were associated with the evolution of the macular disease, consisting of an enlargement of the MH and/or the onset of a macular detachment. CONCLUSIONS: A small percentage (6.26%) of highly myopic eyes may develop an MH in the absence of visual symptoms. The absence of symptoms could be related to the localization of the hole in a juxtafoveal area. Its evolution in a symptomatic MH seems to be related to the presence of epiretinal tissue, younger age, and the degree of myopia.

Retinal detachment associated with macular hole in high myopia: using the vitreous anatomy to optimize the surgical approach.

PURPOSE: To evaluate the efficacy of different surgical strategies on the postoperative outcomes of retinal detachments (RDs) associated with macular holes (MHs) in high myopia. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: The study included 120 phakic, highly myopic eyes (mean degree of myopia, -22.2+/-4.80 diopters) with RDs and MHs that underwent surgical repair. The patients were divided into 2 groups. Group 1 consisted of 60 eyes with a posterior vitreous detachment (PVD). Mean preoperative visual acuity (VA) was 20/200+/-20/500. Group 2 consisted of 60 eyes with posterior vitreous schisis (PVS). The mean preoperative VA was 20/152+/-20/333. The minimum follow-up was 6 months. INTERVENTION: The surgical approach was chosen on the basis of the clinical characteristics. Twenty-five eyes of group 1 underwent pneumoretinopexy (group 1A), whereas 35 eyes of group 1 were repaired with vitrectomy (group 1B). Forty-nine eyes of group 2 underwent pars plana vitrectomy (group 2A), whereas 11 eyes of group 2 underwent scleral buckling of the macula (group 2B). MAIN OUTCOME MEASURES: Anatomic attachment of the retina and VA. RESULTS: Retinal reattachment at 6 months was achieved in 23 of 25 (92%) eyes of group 1A, 31 of 35 (88.5%) eyes of group 1B, 45 of 49 (91.8%) eyes of group 2A, and 8 of 11 (72.7%) eyes of group 2B. A significant (P<0.01) improvement of postoperative VA with respect to the preoperative values was observed in all groups. The greatest percentage improvement in postoperative VA was observed in groups 1A and 1B eyes. CONCLUSIONS: Different surgical approaches can be used to repair myopic RD associated with an MH. The choice between different surgical techniques may depend on vitreoretinal relationships, the extent of chorioretinal atrophic areas, and presence of posterior staphyloma. In our study, eyes with a PVD had significantly better visual outcomes than detachments in eyes with PVS.