Simultaneous and Bilateral Non-Arteritic Anterior Ischaemic Optic Neuropathy and Acute Angle-Closure.

Non-arteritic anterior ischaemic optic neuropathy (NAION) is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. NAION is caused by complex mechanisms that lead to optic nerve head hypoperfusion and is frequently associated with cardiovascular risk factors like type 2 diabetes mellitus (DM2) and hypertension. An attack of acute angle-closure (AAC) occurs when the trabecular meshwork is blocked with peripheral iris that causes an abrupt rise in intraocular pressure, which can trigger a decrease in optic nerve head perfusion. We present a case with simultaneous and bilateral AAC and NAION in association with uncontrolled DM2.

Risk Factors for Visual Field Deterioration in the United Kingdom Glaucoma Treatment Study.

PURPOSE: The United Kingdom Glaucoma Treatment Study (UKGTS) investigated the visual field (VF)-preserving effect of medical treatment in open-angle glaucoma (OAG). The objective of this analysis was to identify risk factors associated with VF deterioration. DESIGN: Randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Five hundred sixteen participants with previously untreated OAG were recruited prospectively in 10 United Kingdom centers. METHODS: Eligibility criteria were modeled on those for the Early Manifest Glaucoma Trial. Study participants were randomized to either latanoprost 0.005% or placebo eye drops. The observation period was 2 years and involved, among other procedures, VF testing and intraocular pressure (IOP) measurement at 11 scheduled visits, with clustering of tests at baseline, 18 months, and 24 months. Guided progression analysis pattern deviation maps were used to determine VF deterioration. Cox regression was used to compute the hazard ratios (HRs) and respective 95% confidence intervals (CIs) while accounting for the correlation within sites. Model selection was guided by backward stepwise selection conducted on the model containing all variables that were significant at the 0.2 level in the univariate analysis. Follow-up variables that showed collinearity with baseline values were not retained in the final model. MAIN OUTCOME MEASURE: Time to VF deterioration. RESULTS: Treatment with latanoprost reduced the HR, for VF deterioration by 58% (HR, 0.42; 95% CI, 0.27-0.67; P = 0.001). Factors associated with deterioration were bilateral disease (HR, 1.59 for yes vs. no; 95% CI, 1.02-2.50; P = 0.041), higher baseline IOP (HR, 1.07 per mmHg; 95% CI, 1.02-1.12; P = 0.008), and disc hemorrhage at visit 1 (HR, 2.08; 95% CI, 1.07-4.04; P = 0.030). Smoking (current or previous) was associated with a reduced HR, for VF deterioration (HR, 0.59; 95% CI, 0.37-0.93; P = 0.023). No other evaluated factors were found to be statistically significant in the multivariable analysis. CONCLUSIONS: In the UKGTS, treatment with latanoprost halved VF deterioration risk. Bilateral disease, higher IOP, and disc hemorrhage were confirmed as risk factors for deterioration; smoking history seemed to be protective against VF deterioration.

Double-bellied medial rectus muscle in a patient with Down syndrome and congenital esotropia.

A 13-year-old male with Down syndrome, pseudophakic secondary to congenital cataract presented with esotropia. During bilateral medial rectus recession, a unilateral two-bellied right medial rectus was identified and recessed successfully with complete resolution of the deviation. Clinicians facing a two-bellied medial rectus can consider continuing with their surgical plan.

Expression of growth hormone and growth hormone receptor genes in human eye tissues.

In humans, the polygenic growth hormone (GH) locus is located on chromosome 17 and contributes with three types of proteins: pituitary GH which consists of at least two isoforms one of 22 kDa and the other of 20 kDa, placental GH, which also exhibits isoforms, and chorionic somatomammotropin hormone (CSH). While pituitary GH results from the expression of the GH-1 (GH-N) gene, placental GH is produced by the expression of the GH-2 (GH-V) gene and CSH is contributed by expression of the CSH-1 and CSH-2 genes. The location where GH-1 is expressed is the anterior pituitary and the rest of the genes in the locus are expressed in placenta. On the other hand, expression and synthesis of GH in extra-pituitary tissues, including the eye, has been recently described. However, the physiological role of GH in the eye has not yet been elucidated, although a possible neuroprotective role has been hypothesized. Thus, we analyzed GH-1, GH-2, CSH1/2, Pit-1, GHR, GHRH, GHRHR, SST, SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 to elucidate the expression and regulation of the GH locus in the human eye. Through qPCR analysis, we only found evidence of GH-1 expression in retina, choroid and trabecular meshwork; its transcript turned out to be the same as pituitary GH mRNA found in major species, and no splicing variants were detected. PIT1 was absent in all the ocular tissues implying an independent GH-1 expression mechanism. We found evidence of GHR in the cornea, choroid coat and retina. These results suggest autocrine and/or paracrine regulation, possibly exerted by GHRH and SSTs (since their mRNAs and receptors were found predominantly in retinal, choroidal and corneal tissues) since expression of both molecules was detected in different ocular tissues, as well as in the same tissues where GH-1 expression was confirmed. Our results add solid evidence about the existence of a regulatory local system for GH expression and release in the human eye.

Expression of growth hormone gene in the baboon eye.

The human growth hormone (GH) locus is comprised by two GH (GH1 and GH2) genes and three chorionic somatomammotropin (CSH1, CSH2 and CSH-L) genes. While GH1 is expressed in the pituitary gland, the rest are expressed in the placenta. However, GH1 is also expressed in several extrapituitary tissues, including the eye. So to understand the role of this hormone in the eye we used the baboon (Papio hamadryas), that like humans has a multigenic GH locus; we set up to investigate the expression and regulation of GH locus in adult and fetal baboon ocular tissues. We searched in baboon ocular tissues the expression of GH1, GH2, CSH1/2, Pit1 (pituitary transcription factor 1), GHR (growth hormone receptor), GHRH (growth hormone releasing hormone), GHRHR (growth hormone releasing hormone receptor), SST (somatostatin), SSTR1 (somatostatin receptor 1), SSTR2 (somatostatin receptor 2), SSTR3 (somatostatin receptor 3), SSTR4 (somatostatin receptor 4), and SSTR5 (somatostatin receptor 5) mRNA transcripts and derived proteins, by qPCR and immunofluorescence assays, respectively. The transcripts found were characterized by cDNA cloning and sequencing, having found only the one belonging to GH1 gene, mainly in the retina/choroid tissues. Through immunofluorescence assays the presence of GH1 and GHR proteins was confirmed in several retinal cell layers. Among the possible neuroendocrine regulators that may control local GH1 expression are GHRH and SST, since their mRNAs and proteins were found mainly in the retina/choroid tissues, as well as their corresponding receptors (GHRH and SSTR1-SSTR5). None of the ocular tissues express Pit1, so gene expression of GH1 in baboon eye could be independent of Pit1. We conclude that to understand the regulation of GH in the human eye, the baboon offers a very good experimental model.

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) expression profile in primates (human and baboon).

BACKGROUND: The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. OBJECTIVE: The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. METHODS: OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. RESULTS: OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. CONCLUSIONS: Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.

Clinical and surgical implications regarding morphometric variations of the medial wall of the orbit in relation to age and gender.

The ethmoidal foramens are located on the medial wall of the orbit and are key reference points for intraoperative orientation. Detailed knowledge of the anatomy, bony landmarks and morphometric characteristics of the medial wall of the orbit is essential for various surgical procedures. The aim of this study was to determine the morphometric variations in the medial wall of the orbit and establish significant variations regarding age and gender. A total of 110 orbits were analyzed and subdivided by age (over or under 40 years) and gender. The distances of the medial wall of the orbit between the anterior lacrimal crest, the ethmoidal foramen, the optic canal and the interforamina were determined. Safe surgical areas were sought. Statistical tests were used to determine the differences between groups. In men, there is a safe surgical area proximal to the anterior and posterior ethmoidal foramen. In women, this area is in the posterior third of the medial wall of the orbit between the posterior ethmoidal foramen and the optic canal. Regarding variation according to age, the results of this study suggested that the anteroposterior diameter of the medial wall increases with age. This study showed that the anteroposterior total length of the medial orbit wall is similar between genders of similar age, increases with age, and has significant variations in the distances between the various structures that make up the medial orbit wall with regard to gender and age.

Conjunctival infection with Chlamydia trachomatis in sexual partners of patients with adult inclusion conjunctivitis.

To compare the incidence of conjunctival infection with Chlamydia trachomatis in sexual partners of patients with newly diagnosed adult inclusion conjunctivitis (AIC) and a control group with healthy eyes. We also compare the observed signs and symptoms of conjunctival infection in patients with newly diagnosed AIC and their sexual partners. We performed a prospective comparative case-control study between patients with newly diagnosed AIC confirmed with direct fluorescent antibody (DFA) (n = 11), their sexual partners (n = 11), and a control group of healthy subjects (n = 11). Clinical history, physical examination, and a DFA test for C. trachomatis of a conjunctival scrapping from the tarsal conjunctiva were performed in all patients. A significantly higher frequency of positive DFA tests for C. trachomatis was observed in the sexual partner group (n = 8, 73 %) compared with the healthy control group (n = 2, 18.2 %) (P = 0.03). Ocular symptoms and signs were observed significantly more often in patients from the confirmed clinically active AIC group (n = 11, 100 %) than in their sexual partners (n = 2, 12.5 %). Sexual partners of patients with AIC are at greater risk of having an asymptomatic conjunctival infection with C. trachomatis than healthy subjects. Sexual partners might be considered a bacterial reservoir and a possible source for chlamydia reinfection. Not treating sexual partners might increase the probability of reinfection. More extended studies with a greater sample size should be done.

A New Case Report of Traboulsi Syndrome: A Literature Review and Insights Into Genotype-Phenotype Correlations.

Traboulsi syndrome is a rare genetic disorder characterized by facial dysmorphism, lens subluxation, anterior segment anomalies, and spontaneous filtering blebs. The syndrome is due to mutations in the ASPH gene, which plays a crucial role in the development and maintenance of the lens. This case report describes the clinical and genetic findings in a Mexican male with Traboulsi syndrome, highlighting the identification of a novel ASPH variant. A 21-year-old male presented with trauma to the right eye while playing soccer. He had a history of lens subluxation and dysmorphic facial features. Ophthalmic examination revealed right eye lens subluxation into the anterior chamber (with signs of a previous episode of acute angle closure) and left eye posterior and inferior lens subluxation with sectorial iris atrophy. Genetic analysis identified a pathogenic ASPH variant (NM_004318.3:c.1892G>A, p.Trp631*) and a novel likely pathogenic variant (deletion of exons 20-21), confirming Traboulsi syndrome. This is the first instance of Traboulsi syndrome in the Mexican population. The absence of spontaneous filtering blebs in this patient supports previous reports of the wide phenotypic variability that could be related to the type of mutation. This novel ASPH variant expands the known genetic heterogeneity of Traboulsi syndrome.

Meibomian Gland Dysfunction and Dropout in Diabetic Patients with Non-Proliferative Diabetic Retinopathy.

This study aims to compare meibomian gland (MG) dropout and MG dysfunction (MGD) between patients with diabetes mellitus (DM) with moderate-severe non-proliferative diabetic retinopathy (NPDR) and patients with no diabetes (NDM). This prospective, transversal, age, and gender-matched case-control study included 98 DM and 106 NDM eyes. Dry eye disease (DED) and MGD evaluations were performed, including meibography (Keratograph 5M®). The objective MG dropout percentage was obtained by analyzing meibography images with ImageJ software (v. 1.52o, National Institutes of Health, Bethesda, MD, USA) and was subsequently graded with Arita's meiboscore. The DM duration was 18 ± 9 years. The mean meiboscore (3.8 ± 0.8 vs. 3.4 ± 1.0, p = 0.001), meiboscore severity (p = 0.016), and MG dropout (45.1 ± 0.1% vs. 39.0 ± 0.4%, p < 0.001) were greater in DM than in NDM. All patients showed MG dropout (meiboscore > 1). Lower eyelids showed greater MG dropout in both groups. A correlation with age (r = 0.178, p = 0.014) and no correlations with DM duration or gender (p > 0.005) were observed. Patients with diabetes showed greater corneal staining (1.7 ± 1.3 vs. 0.9 ± 1.1; p < 0.001), reduced corneal sensitivity (5.4 ± 1.1 vs. 5.9 ± 0.4; p < 0.001), lower MG expressibility (3. 9 ± 1.6 vs. 4.4 ± 2.1; p = 0.017), and worse meibum quality (1.9 ± 0.8 vs. 1.7 ± 0.5; p = 0.019). Tear breakup time, osmolarity, MMP-9, Schirmer, and the Ocular Surface Disease Index showed no significant differences. In conclusion, patients with DM with NPDR have greater MG dropout and meiboscore, as well as more severe MGD and DED parameters than persons with NDM.

Face Mask and Tear Film Stability: A Pilot Study of the Objective Measurement of Tear Break-Up Time.

(1) Background: Mask-associated dry eye (MADE) has been associated with increased dry eye symptoms, apparently due to reduced tear break-up time (TBUT). This study aimed to determine the short-term impact of surgical face mask (FM) on tear film stability by measuring non-invasive tear break-up time (NIBUT). (2) Methods: Twenty-six healthy participants had NIBUT evaluated without FM, with surgical FM and with a surgical FM secured to the skin with adhesive tape (TFM). NIBUT-first was measured with Keratograph 5M (K5M, Oculus, Wetzlar, Germany). Each participant had NIBUT measured in four sessions on four consecutive days. Session 1: without FM vs. with FM. Session 2: with FM vs. without FM. Session 3: without FM vs. with TFM. Session 4: with TFM vs. without FM (3). The time between each measured setting was 2 min. Results: The mean ± SD NIBUT without FM was 8.9 ± 3.7, with FM 10.2 ± 4.1, and with TFM 8.4 ± 3.8 s. No significant differences were observed in NIBUT in any of the evaluated settings: without FM vs. with FM (p = 0.247), without FM vs. with TFM (p = 0.915), and with FM vs. with TFM (p = 0.11). (4) Conclusions: This study did not find a significant short-term effect of FM on NIBUT. Other variables or longer periods of exposure might trigger the symptoms and ocular surface alterations in MADE.

Optic nerve abnormalities in female-restricted Wieacker-Wolff syndrome by a novel variant in the ZC4H2 gene.

BACKGROUND: Wieacker-Wolff syndrome is an ultra-rare disease with X-linked inheritance characterized by arthrogryposis, intellectual disability, microcephaly, and distal limb muscle atrophy. Ophthalmic abnormalities such as ptosis, strabismus, and oculomotor apraxia have been reported in half of the patients. Wieacker-Wolff syndrome female-restricted (WRWFFR) is an even rarer disease recently used for females with a more severe phenotype. MATERIALS AND METHODS: Clinical geneticist and ophthalmic examination, neuroimaging, and exome sequencing. RESULTS: A 4 years-old girl with developmental and language delay, microcephaly, camptodactyly, digital pads, and arthrogryposis was identified by the clinical geneticist. Ophthalmic examination revealed deep-set eyes, high hyperopic astigmatism in both eyes, and reduced retinal nerve fiber layer thickness measured by optical coherence tomography. Exome sequencing identified a novel, probably pathogenic variant in the ZC4H2 gene NM_018684.3:c.145A>T p. (Lys49*) in heterozygosis. DISCUSSION: WRWFFR is an ultra-rare disease with X-linked inheritance by variants in the ZC4H2 gene. This case reports a girl with a novel nonsense variant in the ZC4H2 gene and a severe phenotype; previous reports have identified WRWFFR in females with large deletions and nonsense mutations which could explain the manifestations in the current case report. A complete ophthalmic examination should be considered in patients with WRWFFR to detect the possibly associated optic nerve involvement and other previously described manifestations such as ptosis and strabismus.

Predicting Visual Fields From Optical Coherence Tomography via an Ensemble of Deep Representation Learners.

PURPOSE: To develop and validate a deep learning method of predicting visual function from spectral domain optical coherence tomography (SD-OCT)-derived retinal nerve fiber layer thickness (RNFLT) measurements and corresponding SD-OCT images. DESIGN: Development and evaluation of diagnostic technology. METHODS: Two deep learning ensemble models to predict pointwise VF sensitivity from SD-OCT images (model 1: RNFLT profile only; model 2: RNFLT profile plus SD-OCT image) and 2 reference models were developed. All models were tested in an independent test-retest data set comprising 2181 SD-OCT/VF pairs; the median of ∼10 VFs per eye was taken as the best available estimate (BAE) of the true VF. The performance of single VFs predicting the BAE VF was also evaluated. The training data set comprised 954 eyes of 220 healthy and 332 glaucomatous participants, and the test data set, 144 eyes of 72 glaucomatous participants. The main outcome measures included the pointwise prediction mean error (ME), mean absolute error (MAE), and correlation of predictions with the BAE VF sensitivity. RESULTS: The median mean deviation was -4.17 dB (-14.22 to 0.88). Model 2 had excellent accuracy (ME 0.5 dB, SD 0.8) and overall performance (MAE 2.3 dB, SD 3.1), and significantly (paired t test) outperformed the other methods. For single VFs predicting the BAE VF, the pointwise MAE was 1.5 dB (SD 0.7). The association between SD-OCT and single VF predictions of the BAE pointwise VF sensitivities was R2 = 0.78 and R2 = 0.88, respectively. CONCLUSIONS: Our method outperformed standard statistical and deep learning approaches. Predictions of BAEs from OCT images approached the accuracy of single real VF estimates of the BAE.

Reduced corneal endothelial cell density after toxic anterior segment syndrome (TASS) caused by inadvertent intraocular ointment migration: A case report.

INTRODUCTION AND IMPORTANCE: Toxic anterior segment syndrome (TASS) is an acute sterile inflammation of the anterior segment which may occur after surgery. This case presents endothelial cell density (ECD) loss due to months of TASS caused by intraocular migration of ocular ointment. The chronicity of this case and the clinical consequences are rare in the literature. CASE PRESENTATION: A Colombian 71-year-old man developed TASS secondary to intraocular ointment migration after uneventful cataract surgery with phacoemulsification and intraocular lens placement in the capsular bag. The main complaint for the patient was a chronic red eye, no pain or visual disturbance were reported, rheumatologic diseases were discarded. It was documented the presence of intraocular ointment in the anterior chamber, over the iris and in the anterior chamber angle. The ECD was reduced secondary to TASS and the long-term presence of ointment moving in the anterior chamber, so it had to be removed. CLINICAL DISCUSSION: It is important to avoid using ocular ointment after intraocular surgeries to avoid the risk of ointment migration into the anterior chamber. Intraocular ointments should be removed promptly to reduce ECD loss as documented in the present case report in which after ointment elimination ECD remains stable for 7 years. CONCLUSION: Topical ointments should not be used after routine cataract surgery because of the risk of intraocular ointment migration and subsequent risk of developing TASS and reduced ECD.

Cyclodiode Laser as the First Surgical Approach in Childhood Glaucoma Under the Age of 8 Years.

PRCIS: Cyclodiode as a primary treatment for childhood glaucoma patients younger than 8 years has a 12-month success rate of 55.24%. It can delay the need for penetrating glaucoma surgery. PURPOSE: The purpose of this study was to evaluate the treatment outcome of cyclodiode laser in childhood glaucoma for patients under the age of 8 years. DESIGN: This was a retrospective, consecutive, noncomparative case series. PARTICIPANTS: All childhood glaucoma patients who underwent cyclodiode from March 2005 to January 2017 as a primary surgical treatment under the age of 8 years. METHODS: A retrospective review of the medical records of consecutive patients who underwent cyclodiode by a single surgeon. MAIN OUTCOME MEASURES: Success for single-diode intervention was defined as intraocular pressure (IOP) (>6 wk postoperative) ≤21 mm Hg with antiglaucoma medications and ≥20% IOP reduction, no further glaucoma surgery including cyclodiode, no loss of perception of light, and no major complications. Success for multiple-diode interventions was defined similar to the single diode, except that repeated cyclodiode is not considered a failure. RESULTS: In all, 59 eyes of 43 patients were studied. The most common diagnosis was aphakic glaucoma. The mean age at cyclodiode treatment was 2.7 years (SD=2.2). Fifty-six percent of the patients were under 3 years. Success rates at 12 months after the procedure were 46.67% and 55.24% for single-diode and multiple-diode interventions, respectively. An IOP of >20 mm Hg 6 weeks after a cyclodiode session is a significant risk factor for failure with an hazard ratio of 2.41 (95% confidence interval: 1.00-5.81; P=0.05). Among the operated eyes, the surgeon could avoid further glaucoma surgery in 67.8% of the eyes during the first year after single or multiple cyclodiode sessions. None of the eyes experienced phthisis bulbi, hypotony, and severe uveitis. CONCLUSIONS: Cyclodiode laser in childhood glaucoma patients under the age of 8 years can be considered a safe alternative for glaucoma patients who can have a high risk of surgical complications. Performing cyclodiode laser can delay the need for penetrating glaucoma surgery. The IOP at 6 weeks may be a good predictor for the treatment outcome.

OCT Signal Enhancement with Deep Learning.

PURPOSE: To establish whether deep learning methods are able to improve the signal-to-noise ratio of time-domain (TD) OCT images to approach that of spectral-domain (SD) OCT images. DESIGN: Method agreement study and progression detection in a randomized, double-masked, placebo-controlled, multicenter trial for open-angle glaucoma (OAG), the United Kingdom Glaucoma Treatment Study (UKGTS). PARTICIPANTS: The training and validation cohort comprised 77 stable OAG participants with TD OCT and SD OCT imaging at up to 11 visits within 3 months. The testing cohort comprised 284 newly diagnosed OAG patients with TD OCT images from a cohort of 516 recruited at 10 United Kingdom centers between 2007 and 2010. METHODS: An ensemble of generative adversarial networks (GANs) was trained on TD OCT and SD OCT image pairs from the training dataset and applied to TD OCT images from the testing dataset. Time-domain OCT images were converted to synthesized SD OCT images and segmented via Bayesian fusion on the output of the GANs. MAIN OUTCOME MEASURES: Bland-Altman analysis assessed agreement between TD OCT and synthesized SD OCT average retinal nerve fiber layer thickness (RNFLT) measurements and the SD OCT RNFLT. Analysis of the distribution of the rates of RNFLT change in TD OCT and synthesized SD OCT in the two treatment arms of the UKGTS was compared. A Cox model for predictors of time-to-incident visual field (VF) progression was computed with the TD OCT and the synthesized SD OCT images. RESULTS: The 95% limits of agreement were between TD OCT and SD OCT were 26.64 to -22.95; between synthesized SD OCT and SD OCT were 8.11 to -6.73; and between SD OCT and SD OCT were 4.16 to -4.04. The mean difference in the rate of RNFLT change between UKGTS treatment and placebo arms with TD OCT was 0.24 (P = 0.11) and with synthesized SD OCT was 0.43 (P = 0.0017). The hazard ratio for RNFLT slope in Cox regression modeling for time to incident VF progression was 1.09 (95% confidence interval [CI], 1.02-1.21; P = 0.035) for TD OCT and 1.24 (95% CI, 1.08-1.39; P = 0.011) for synthesized SD OCT. CONCLUSIONS: Image enhancement significantly improved the agreement of TD OCT RNFLT measurements with SD OCT RNFLT measurements. The difference, and its significance, in rates of RNFLT change in the UKGTS treatment arms was enhanced and RNFLT change became a stronger predictor of VF progression.