Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.

Cross-sectional associations of dietary intake with hearing and vision capacities and potential mediation effect of inflammation in older adults: the COGFRAIL study.

BACKGROUND: Considering their prevalence and burden, information on the sensory impairment etiology is essential. Links between nutrition and sensory impairment through inflammation have been suggested. Although the decline in sensory capacities is age-related, few research included a geriatric population. AIMS: Exploring the associations of nutrition with sensory capacities and test inflammation as a mediator among cognitively and physically impaired older adults. METHODS: Cross-sectional data from the COGFRAIL cohort, including 164 participants with no hearing aid and 20 participants wearing no visual aid. Hearing was evaluated using the Hearing Handicap Inventory for the Elderly-screening version (on 40 points, the lower the better), and the Monoyer chart (one to ten out of ten points, the higher the better), and the Parinaud scale (from 1.5, the best, to 28 points, the worst) assessed distant and near vision, respectively. Dietary intake was assessed through a diet history interview and inflammation was measured by the C-Reactive Protein level. Multivariate linear regressions were performed and Structural Equation Modeling (SEM) framework was used to explore the potential mediation effect of inflammation on the diet-hearing relationships. RESULTS: None of the nutrients was significantly associated with hearing acuity in the regressions or the SEM model. Regarding vision, a higher intake of saturated fatty acids was related to lower long-distance visual acuity, and greater Omega-3 consumption was associated with better near-vision capacity. DISCUSSION: No nutrient was associated with hearing capacity and relationships between fatty acids quality and vision acuity were suggested. CONCLUSION: These exploratory results require further investigations.

First-line management of necrotizing herpetic retinitis by prioritizing the investigation of immune status and prognostic factors for poor visual outcomes.

PURPOSE: To review management, treatment, and outcomes of patients with necrotizing herpetic retinitis (NHR) to propose an algorithm for first-line management of NHR. METHODS: Retrospective evaluation of a series of patients with NHR at our tertiary center between 2012 and 2021 using demographic, clinical, ophthalmologic, virological, therapeutic, and prognostic characteristics was performed. Patients were classified by NHR type: acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis. RESULTS: Forty-one patients with NHR were included: 59% with ARN, 7% with PORN, and 34% with CMV retinitis. All patients with CMV retinitis and PORN were immunocompromised versus 21% of patients with ARN. CMV infection was found in 14 (34%) patients, varicella zoster virus infection in 14 (34%) patients, herpes simplex virus type 2 infection in 8 (20%) and type 1 infection in 5 (12%) patients. Intravenous antiviral therapy was received by 98% of patients and intravitreal antiviral injections by 90% of patients. The overall complication rate during follow-up was 83% of eyes. Most frequent complications were retinal detachment (33% eyes) and retinal break (29% eyes). Prognostic factors for poor visual outcomes were pre-existing monocular vision loss in contralateral eye among 17% of patients, bilateral NHR in 17% of patients, posterior pole involvement in 46% of eyes, and involvement > 2 retinal quadrants in 46% of eyes. CONCLUSIONS: The visual prognosis of patients with NHR remains poor. Prompt investigation of immune status and presence of factors justifying intravitreal antiviral injections must be prioritized to initiate and adapt management while awaiting causative virus confirmation.

First evidence of SOX2 mutations in Peters' anomaly: Lessons from molecular screening of 95 patients.

Peters' anomaly (PA) is a rare anterior segment dysgenesis characterized by central corneal opacity and irido-lenticulo-corneal adhesions. Several genes are involved in syndromic or isolated PA (B3GLCT, PAX6, PITX3, FOXE3, CYP1B1). Some copy number variations (CNVs) have also been occasionally reported. Despite this genetic heterogeneity, most of patients remain without genetic diagnosis. We retrieved a cohort of 95 individuals with PA and performed genotyping using a combination of comparative genomic hybridization, whole genome, exome and targeted sequencing of 119 genes associated with ocular development anomalies. Causative genetic defects involving 12 genes and CNVs were identified for 1/3 of patients. Unsurprisingly, B3GLCT and PAX6 were the most frequently implicated genes, respectively in syndromic and isolated PA. Unexpectedly, the third gene involved in our cohort was SOX2, the major gene of micro-anophthalmia. Four unrelated patients with PA (isolated or with microphthalmia) were carrying pathogenic variants in this gene that was never associated with PA before. Here we described the largest cohort of PA patients ever reported. The genetic bases of PA are still to be explored as genetic diagnosis was unavailable for 2/3 of patients. Nevertheless, we showed here for the first time the involvement of SOX2 in PA, offering new evidence for its role in corneal transparency and anterior segment development.

Evaluation of the Effects of Vitrectomy with Primary Epiretinal Membrane Peel on Optical Quality Using Double-Pass Aberrometry.

INTRODUCTION: We performed a prospective, single-center, cohort study in order to evaluate the effects of vitrectomy with epiretinal membrane (ERM) peel on optical quality in patients with primary ERM. METHODS: Thirty patients treated for primary ERM by vitrectomy with ERM peel were included from our tertiary university hospital ophthalmology department. The main study outcome was a variation in optical quality parameters measured using the HD Analyzer™ between preoperative and 2-month postoperative evaluations in operated eyes. Optical quality parameters comprised point spread function (PSF) width at 10% and 50%, objective scatter index (OSI), and modulation transfer function (MTF) cutoff. Contralateral non-operated eyes were used as an internal control for measurement reproducibility. RESULTS: Mean PSF width at 10% (42.22 vs. 27.37 arc/min; p = 0.0002) and mean OSI (3.32 vs. 2.32; p = 0.0003) were significantly improved between pre- versus postoperative evaluations. Mean PSF width at 50% and mean MTF cutoff showed no changes. Subgroup analysis according to crystalline lens status gave similar results, demonstrating that improvements in mean PSF width at 10% and OSI were not lens-related. Non-operated eyes showed no changes in any of the parameters analyzed. CONCLUSION: Reduced light scattering measured by OSI indicates improved optical quality following vitrectomy with ERM peel among patients with primary ERM. OSI measurement could thus be a new parameter of interest in the preoperative assessment of primary ERM and other pre-vitrectomy assessments.

RECURRENCES OF RETINAL DETACHMENT AFTER RETINECTOMY: Causes and Outcomes.

PURPOSE: To evaluate the different mechanisms of retinal detachment recurrence after retinectomy for rhegmatogenous retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR) and to study its outcome and prognosis. METHODS: Retrospective, multicenter study conducted between January 2009 and November 2016. Retrospective review of 56 patients with recurrent RD (RRD) after a first relaxing retinectomy. RESULTS: The secondary retinal attachment rate was 58.9% (33/56 cases). The various mechanisms of RRD were mainly related to PVR (52/56 cases: 93%). This PVR was anterior in 10 cases (21%), posterior in 31 cases (60%), and combined anterior and posterior in 11 cases (21%). The RRD mechanism was not PVR in 4 of the 56 cases. Some of the RRD mechanisms were specific to retinectomy: fibrosis of the edge of the retinectomy (26 cases: 46.4%), beyond-the-edge proliferation (8 cases: 14.3%), and severe inferior retinal folding (2 cases: 3.6%). In the 2 cases of severe inferior retinal folding, the retina could not be reattached. The anatomical outcome and the mechanism of RRD (anterior PVR, posterior PVR, or combined anterior and posterior PVR) were not correlated (P = 0.12). Visual acuity was significantly better only in patients with complete secondary success, that is, having an attached retina after silicone oil removal: mean preoperative visual acuity was 2.01 logarithm of the minimum angle of resolution versus 1.01 logarithm of the minimum angle of resolution postoperatively (P = 0.019). CONCLUSION: Proliferative vitreoretinopathy caused most of the recurrences, and the anatomical outcome did not depend on the type of PVR involved. Only complete secondary success (attached retina after silicone oil removal) was accompanied by visual acuity improvement.

Combining fixation and lateral masking training enhances perceptual learning effects in patients with macular degeneration.

Macular degeneration (MD), a retinal disease affecting central vision, represents the leading cause of visual impairment in the Western world, and MD patients face severe limitations in daily activities like reading and face recognition. A common compensation strategy adopted by these patients involves the use of a region in the spared peripheral retina as a new fixation spot and oculomotor reference (preferred retinal locus, or PRL). Still, peripheral vision is characterized by poorer visual acuity, fixation stability, and larger crowding zones that further hinder processes like object recognition, visual search, and reading. Perceptual learning (PL) has been successfully used to improve visual acuity in mild visual conditions (e.g., presbyopia, amblyopia and myopia), but results in MD are less clear, often showing limited generalization of learning, unlike what is observed in a healthy population. A possible reason is the suboptimal fixation in the PRL that might prevent patients from processing the briefly presented training stimuli. Following this hypothesis, we trained five MD patients and four age- and eccentricity-matched controls with a protocol that combined contrast detection and a task previously used to train fixation stability. Results showed transfer of learning to crowding reduction, reading speed, and visual acuity in both MD patients and controls. These results suggest that in the case of central vision loss, PL training might benefit from the integration of oculomotor components to optimize the effect of training and promote transfer of learning to other visual functions.

First Experience With the ICD 16.5 Mini-Scleral Lens for Optic and Therapeutic Purposes.

OBJECTIVES: To evaluate the success rate, efficacy, and safety of the ICD 16.5 mini-scleral gas permeable (GP) contact lens. METHODS: This prospective study included referred consecutive patients with irregular corneas and severe ocular surface disease (OSD) in treatment failure. All patients were fitted with the ICD 16.5 mini-scleral GP lens. Even though we had some limited experience with scleral lenses, it was our first experience with the ICD 16.5 mini-scleral GP lens. Efficacy was assessed by comparing best-corrected visual acuity (BCVA) with the mini-scleral lens to baseline BCVA. A subjective visual functioning questionnaire (comfort score, visual quality score, handling rating, and wearing time) was administered in a face-to-face structured interview. RESULTS: Thirty-nine eyes of 23 patients with a mean age of 43±16 years were included. Fitting indications were keratoconus (46%), post-penetrating keratoplasty (21%), other irregular astigmatism (15%), and severe OSD (18%). Twenty-five eyes (64%) were successfully fitted with an 18-month follow-up. The mini-scleral GP lens BCVA was 0.16 logarithm of the minimum angle of resolution (logMAR; 20/25) versus a baseline BCVA of 0.44 logMAR (20/63; P<0.001). Comfort and visual quality scores were 8.5/10 and 7.5/10, respectively. No complications were detected in 96% of the eyes (95% confidence interval, 76.1%-99.4%). One eye experienced corneal graft swelling. CONCLUSIONS: The present findings suggest that the ICD 16.5 mini-scleral GP lens is an effective and safe alternative for managing challenging corneas in a therapeutic impasse.

Preliminary study of the safety and efficacy of medium-chain triglycerides for use as an intraocular tamponading agent in minipigs.

PURPOSE: To date, only silicone oils and gases have the appropriate characteristics for use in vitreo-retinal surgery as vitreous substitutes with intraocular tamponading properties. This preliminary study evaluated the safety and efficacy of medium-chain triglycerides (MCTs) for use as a tamponading agent in minipigs. METHODS: In 15 minipigs, 15 right eyes underwent vitrectomies followed by injection of MCT tamponade (day 1). Two groups were defined. In Group A (ten eyes), the surgical procedure before MCT injection included induced rhegmatogenous retinal detachment (RRD), retina flattening, and retinopexy. In Group B (five eyes), MCT was injected without inducing RRD; in these eyes, MCT was removed on day 90. Pigs were sacrificed on day 45 (Group A) or 120 (Group B). Eyes were examined on days 1, 5, 15, and 45 in both groups and on days 90 and 120 in Group B. In Group B only, we performed bilateral electroretinography examinations on days 1 and 120, and histological examinations of MCTs and controlateral eyes were performed after sacrifice. RESULTS: In Group A eyes (n = 9; one eye was non-assessable), on day 45, the retina was flat in seven eyes and two RRD detachments were observed in insufficiently MCT-filled eyes. In Group B, electroretinography showed no significant differences between MCT eyes and controls on days 1 or 120. Histological analyses revealed no signs of retinal toxicity. CONCLUSIONS: This study showed that MCT tamponade seems to be effective and safe; however, additional studies are needed before it becomes commonly used as a tamponading agent in humans.

Mutations in SCO2 are associated with autosomal-dominant high-grade myopia.

Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of -22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SC02 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development.

Relationship between induced spherical aberration and depth of focus after hyperopic LASIK in presbyopic patients.

OBJECTIVE: To evaluate to what extent the modification of corneal asphericity to induce spherical aberration (SA) can improve the depth of focus and to determine whether preoperative adaptive optics assessment (Voptica SL) can predict an optimal SA value for each patient. DESIGN: Comparative, prospective clinical trial with paired eye control. PARTICIPANTS: Patients ≥45 years old who are hyperopic from +1.00 to +2.50 diopters (D), with eyes suitable for LASIK surgery. INTERVENTION: Bilateral hyperopic LASIK surgery using a 200-Hz Allegretto excimer laser. The dominant eye was operated using a conventional profile. The nondominant eye was programmed with an aspheric ablation profile and -0.75 D monovision. MAIN OUTCOME MEASURES: Primary outcome was the correlation between postoperative SA and depth of focus, defined as the pseudo-accommodation value (PAV = [1/reading distance {m}] - minimum addition [D]). Main secondary outcome was the comparison of depth of focus between patients with an induced SA close to the optimal one (group 1), patients with an induced SA far from the optimal one (group 2), and patients for whom SA induction did not increase the depth of focus (control group). RESULTS: We included 76 patients. Between preoperative and postoperative assessment, the mean increase of distance-corrected PAV for near vision was +0.25±0.64 D (P < 0.001) for dominant eyes and +0.63±0.55 D (P < 0.001) for nondominant eyes. As the level of negative or positive postoperative SA increased, PAV for intermediate and near vision increased. Among the 37 eyes that followed the preoperative adaptive optics assessment, the mean PAV increase at near was significantly higher (P < 0.05) in group 1 (0.93±0.50 D) than in group 2 (0.46±0.42 D) and than in the control group (0.35±0.32 D). The mean optimal SA value determined by the dynamic simulation procedure to optimize the depth of focus was -0.18±0.13 µm at 4.5 mm. CONCLUSIONS: Aspheric hyperopic LASIK can increase the depth of focus without impairing far vision, but this benefit would be maximal and reproducible if we could define and achieve an optimal SA value determined by preoperative assessment using an adaptive optics instrument.

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis.

BACKGROUND: Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. METHODS AND RESULTS: A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband's mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. CONCLUSIONS: We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases.

Conventional Epithelial-Off Corneal Crosslinking in Patients With Progressive Keratoconus: 10-Year Outcomes.

PURPOSE: Corneal crosslinking (CXL) is the standard treatment of progressive keratoconus (KC). We evaluated the safety and 10-year outcomes of conventional "epithelial-off" CXL for progressive KC for the first time in a cohort in France. METHODS: We conducted a retrospective review of patients undergoing conventional CXL (Dresden protocol) in our tertiary ophthalmology department from 2006 to 2011 with 10-year follow-up. The primary outcome was change in preoperative versus postoperative keratometry measured by maximum keratometry (Kmax), steep keratometry (K2), flat keratometry (K1), mean keratometry (Km), and topographic cylinder. Secondary outcomes were changes in visual and refractive outcomes. We report postoperative complications and adverse events. RESULTS: Eighty-nine eyes from 76 patients (67% male patients, mean age 22.7 ± 7.6 years) were included. Mean Kmax (-2.31 ± 2.98 diopters (D); P < 0.00001), K2 (-2.07 ± 3.15 D; P < 0.00001), K1 (-1.00 ± 2.29 D; P = 0.00008), Km (-1.53 ± 2.47 D; P < 0.00001), and topographic cylinder (-1.15 ± 2.53 D; P = 0.00004) significantly decreased 10 years after CXL compared with preoperative baseline. Significant decreases were still observed between 5 and 10 years after for mean Kmax, mean K2, mean K1, and mean Km. Mean distance best spectacle-corrected visual acuity and mean manifest refraction spherical equivalent were significantly improved after 10 years versus before CXL. The 10-year rate of repeat CXL was n = 3/76 patients (4%) (all younger than 18 years at first CXL) and of loss of >3 lines in best spectacle-corrected visual acuity was n = 1/76 patients (1%). CONCLUSIONS: Progressive KC was effectively stabilized with a prolonged flattening and maintenance of functional vision improvements after 10 years. Repeat CXL was rare and only required among younger patients.

tRNS boosts visual perceptual learning in participants with bilateral macular degeneration.

Perceptual learning (PL) has shown promise in enhancing residual visual functions in patients with age-related macular degeneration (MD), however it requires prolonged training and evidence of generalization to untrained visual functions is limited. Recent studies suggest that combining transcranial random noise stimulation (tRNS) with perceptual learning produces faster and larger visual improvements in participants with normal vision. Thus, this approach might hold the key to improve PL effects in MD. To test this, we trained two groups of MD participants on a contrast detection task with (n = 5) or without (n = 7) concomitant occipital tRNS. The training consisted of a lateral masking paradigm in which the participant had to detect a central low contrast Gabor target. Transfer tasks, including contrast sensitivity, near and far visual acuity, and visual crowding, were measured at pre-, mid and post-tests. Combining tRNS and perceptual learning led to greater improvements in the trained task, evidenced by a larger increment in contrast sensitivity and reduced inhibition at the shortest target to flankers' distance. The overall amount of transfer was similar between the two groups. These results suggest that coupling tRNS and perceptual learning has promising potential applications as a clinical rehabilitation strategy to improve vision in MD patients.

The Reinforced Treat-and-Extend Protocol for Exudative Age-Related Macular Degeneration: Retrospective Assessment of 24-Month Real-World Outcomes in France.

INTRODUCTION: The aim of this work is to evaluate the real-world outcomes of the reinforced treat-and-extend (RTE) protocol for the treatment of exudative age-related macular degeneration with intravitreal injections of aflibercept or ranibizumab (anti-vascular endothelial growth factor therapies). METHODS: This was a retrospective review of patients from two tertiary ophthalmology centers in France initiating the RTE protocol between February 2018 and June 2021. The primary outcome was change in best-corrected visual acuity (BCVA) after 24 months. Secondary outcomes were change in central retinal thickness (CRT), recurrence, and management-related factors (injection interval, number of injections/consultations). Outcomes were additionally evaluated after protocol changes (strict versus modified RTE protocol groups). RESULTS: Sixty-eight patients (72 eyes) were included (68% females; mean age 82.2 ± 7.8 years). After 24 months, mean BCVA significantly improved (65.22 ± 14 vs. 71.96 ± 13 Early Treatment Diabetic Retinopathy Study letters; p < 0.001) and CRT significantly decreased (388.6 ± 104 vs. 278.8 ± 51 µM; p < 0.001) with 21% of eyes showing signs of exudation. Over the 24 months, a mean total of 14.9 ± 4.0 injections and 8.6 ± 1.4 consultations were performed. Mean 24-month injection interval was 7.9 ± 2.3 weeks. Initial and 24-month ophthalmic outcomes for eyes in the strict (47%) versus modified (53%) groups were not significantly different, but mean time interval to first recurrence of disease activity was significantly shorter for the modified group (7.3 ± 2.4 vs. 9.9 ± 2.5 weeks; p < 0.001). Patients in the strict RTE group received significantly less injections (13.9 ± 3.6 vs. 16.5 ± 3.9; p = 0.006) and mean 24-month injection interval was significantly longer (9.5 ± 2.7 vs. 6.5 ± 2.1 weeks; p < 0.001). Consultation number was similar (8.5 ± 1.9 vs. 8.8 ± 1.6; p = 0.93). Treatment with aflibercept versus ranibizumab did not influence ophthalmic or management outcomes. CONCLUSIONS: The RTE protocol, even when modified, reduced consultations but improved ophthalmic outcomes. The RTE protocol could reduce hospital visits and overall burden while also encouraging better patient compliance. Video Abstract available for this article. VIDEO ABSTRACT: Vincent Soler and François-Philippe Roubelat summarize the Reinforced Treat-and-Extend Protocol and main results (MP4 225022 KB).

Neuro-ophthalmological changes in healthy females exposed to a 5-day dry immersion: a pilot study.

After exposure to microgravity, astronauts undergo microgravity-induced thoraco-cephalic fluid shift, which may lead to ocular changes called "spaceflight associated neuro-ocular syndrome" (SANS). The onset of SANS may be multifactorial, including a potential elevation in intracranial pressure. Moreover, little is known about the impact of spaceflight on SANS in women due to the fact that fewer female astronauts have spent time in long-term missions. The objective is to determine whether similar ophthalmological changes occur in healthy women after short-term exposure to microgravity. The auto-refractometer was used to determine objective refraction. The best corrected distance visual acuity was assessed with a Monoyer chart. The ocular axial length was assessed using optical biometry. The applanation tonometry was used to determine intraocular pressure. Peripapillary retinal nerve fibre layer thickness (pRNFLT), macular total retinal thickness, and ganglion cell complex (GCC) were measured using optical coherence tomography. Ocular axial length is reduced after DI. pRNFL is thickest after DI specifically in the temporal, temporal-inferior, and nasal-inferior quadrants. Macular total retinal at the inferior quadrant of the 6-mm ring is thickest after DI. Global GCC is thinnest after DI. In this study, 5 days of DI induces slight but significant ophthalmological changes in women. However, these subtle changes do not correspond to criteria defined in SANS.

Mutation in collagen II alpha 1 isoforms delineates Stickler and Wagner syndrome phenotypes.

PURPOSE: Stickler syndrome is an arthro-ophthalmopathy with phenotypic overlap with Wagner syndrome. The common Stickler syndrome type I is inherited as an autosomal dominant trait, with causal mutations in collagen type II alpha 1 (COL2A1). Wagner syndrome is associated with mutations in versican (VCAN), which encodes for a chondroitin sulfate proteoglycan. A three-generation Caucasian family variably diagnosed with either syndrome was screened for sequence variants in the COL2A1 and VCAN genes. METHODS: Genomic DNA samples derived from saliva were collected from all family members (six affected and four unaffected individuals). Complete sequencing of COL2A1 and VCAN was performed on two affected individuals. Direct sequencing of remaining family members was conducted if the discovered variants followed segregation. RESULTS: A base-pair substitution (c.258C>A) in exon 2 of COL2A1 cosegregated with familial disease status. This known mutation occurs in a highly conserved site that causes a premature stop codon (p.C86X). The mutation was not seen in 1,142 ethnically matched control DNA samples. CONCLUSIONS: Premature stop codons in COL2A1 exon 2 lead to a Stickler syndrome type I ocular-only phenotype with few or no systemic manifestations. Mutation screening of COL2A1 exon 2 in families with autosomal dominant vitreoretinopathy is important for accurate clinical diagnosis.

Amniotic membrane grafting for a case of bilateral giant full-thickness macular hole in Alport syndrome after cataract surgery.

PURPOSE: To describe the surgical management of bilateral giant full-thickness macular hole with sudden onset two months after cataract surgery in a patient with Alport syndrome. METHODS: Observational, single-case report. RESULTS: A 54-year-old female with a history of Alport syndrome presented with severe bilateral visual loss two months after cataract surgery. The diagnosis of bilateral giant full-thickness macular hole was made. We found the absence of the internal limiting membrane and the inability to lift and peel a continuous posterior hyaloid sheet during surgical management with 25-gauge pars plana vitrectomy (left eye). Amniotic membrane grafting followed by gas tamponade were performed for hole closure. The hole remained closed but vision was poorly restored two months after. CONCLUSION: Cataract surgery in patients with Alport syndrome could promote early development of giant full-thickness macular hole. Collagen defects could underlie internal limiting membrane absence and the inability to properly peel the posterior hyaloid.