Purpose: To determine whether children born to mothers with gestational diabetes mellitus (GDM) are at increased risk to develop of pediatric ophthalmic morbidity. Materials and methods: In this population based cohort study, all deliveries between 1991 and 2014 were included. Congenital malformations, multiple gestations, and patients lacking prenatal care were excluded from analysis. Mothers were defined as either having no GDM, having diet-treated GDM, or medically treated GDM. Outcomes were defined as different ophthalmic morbidities of the offspring until the age of 18. Kaplan–Meier curves were used to compare the cumulative morbidity in each group, and a Cox proportional hazard model was used to control for possible confounders. Results: During the study period, 238,622 deliveries met the inclusion criteria, of those 4.0% (n = 9601) of mothers were diagnosed with GDM treated by diet, and an additional 1.0% (n = 2398) were diagnosed with GDM treated by medication. Offsprings of patients with GDM treated by medication had a higher cumulative incidence of ophthalmic morbidity when compared to the other groups (Kaplan–Meier log rank test p = .038). GDM treated by medication was found to be an independent risk factor for long-term ophthalmic morbidity, in a cox multivariable model (adjusted HR: 1.5, 95%CI: 1.05–2.1, p = .025). Conclusions: Gestational diabetes mellitus treated by medication is associated with an increased risk for long-term pediatric ophthalmic morbidity.

Leber congenital amaurosis (LCA) is a severe retinal degenerative disease that manifests as blindness or poor vision in infancy. The purpose of this study was to clinically characterize and identify the cause of disease in a large inbred Bedouin Israeli tribe with LCA. Thirty individuals of a single kindred, including eight affected with LCA, were recruited for this study. Patients’ clinical data and electroretinography (ERG) findings were collected. Molecular analysis included homozygosity mapping with polymorphic markers and Sanger sequencing of candidate genes. Of the eight affected individuals of the kindred, nystagmus was documented in five subjects and keratoconus in three. Cataract was found in 5 of 16 eyes. Photopic and scotopic ERG performed in 5 patients were extinguished. All affected subjects were nearly blind, their visual acuity ranged between finger counting and uncertain light perception. Assuming autosomal recessive heredity of a founder mutation, studies using polymorphic markers excluded homozygosity of affected individuals at the genomic loci of all previously known genes associated with LCA, except GUCY2D. Sequencing of GUCY2D identified a novel missense mutation (c.2129C>T; p.Ala710Val) resulting in substitution of alanine by valine at position 710 within the protein kinase domain of the retina-specific enzyme guanylate cyclase 1 (GC1) encoded by GUCY2D. Molecular modeling implied that the mutation changes the conformation of the regulatory segment within the kinase styk-domain of GC1 and causes loss of its helical structure, likely inhibiting phosphorylation of threonine residue within this segment, which is needed to activate the catalytic domain of the protein. This is the first documentation of the p.Ala710Val mutation in GC1 and the second ever described mutation in its protein kinase domain. Our findings enlarge the scope of genetic variability of LCA, highlight the phenotypic heterogeneity found amongst individuals harboring an identical LCA mutation, and possibly provide hope for gene therapy in patients with this congenital blinding disease. As the Bedouin kindred studied originates from Saudi Arabia, the mutation found might be an ancient founder mutation in that large community.

Background: Unruptured intracranial aneurysms that cause isolated sixth nerve palsies are usually located extradurally in the cavernous sinus or intradurally as part of fusiform enlargement of the parent artery. Intradural saccular aneurysms of the vertebrobasilar circulation are a rare but life-threatening cause of isolated sixth nerve palsy. We provide documentation of 2 such cases. Methods: Case records of the Neuro-ophthalmology Clinics at the University of Michigan. Results: A 56-year-old woman with an arteriosclerotic risk profile reported new diplopia and had an isolated left sixth nerve palsy caused by an unruptured saccular aneurysm of the anterior inferior cerebellar artery. It was successfully coiled, and the sixth nerve palsy markedly improved. A 62-year-old woman with an arteriosclerotic risk profile and new diplopia had an isolated right sixth nerve palsy caused by a large unruptured vertebral artery aneurysm. It was coiled and later stented and recoiled. These procedures isolated the aneurysm and relieved the sixth nerve palsy. Conclusions: Isolated sixth nerve palsies in these 2 older adult patients with arteriosclerotic risk profiles were caused by unruptured intradural vertebrobasilar aneurysms. This report adds documentation to a rare phenomenon that must be taken into consideration in deciding whether brain imaging is needed in isolated sixth nerve palsy.

Background: Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of acute optic nerve damage. While cardiovascular risk factors such as hypertension, diabetes mellitus, and obstructive sleep apnea are well-established, the association between NAION and states of hypoperfusion is underexplored. This study investigated this potential association. Methods: This retrospective case-control study analyzed all electronic medical records of Clalit Health Services’ patients from 2001 to 2022. Patients diagnosed with NAION were matched in a 1:4 ratio by year of birth and sex, using propensity score analysis to adjust for various comorbidities. Events of hypoperfusion occurring in the month prior to the diagnosis of NAION were categorized into two physiological mechanisms: a decrease in SVR and a decrease in cardiac output due to cardiac dysfunction or diminished preload (attributed to hypovolemia). Conditional logistic regression was used to explore differences between the groups. Results: A total of 1,374 patients diagnosed with NAION and 5,496 matched controls were included in the study. We found a nearly 6.5-fold increase in the likelihood of NAION in association with events of hypoperfusion that occurred in the month period preceding the diagnosis of NAION (odds ratio [OR] 6.48; 95% confidence interval [CI]: 5.05–8.32). In particular, the group of patients with cardiac dysfunction (OR 6.47; 95% CI: 4.63–9.04) and the group with hypovolemia (OR 6.1; 95% CI: 4.08–9.13) emerged as having the most substantial risk factors. The group with decreased Systemic Vascular Resistance (SVR) (OR 4.64; 95% CI: 2.84–7.59) was also strongly related with NAION. Cerebrovascular accident emerged as an independent significant risk factor for NAION (OR 16.1; 95% CI: 10.8–24). Conclusion: Hypoperfusion states are significant, independent risk factors for NAION.

Purpose: While patients with cardiovascular comorbidities are at a higher risk for the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION), it is unclear whether adherence to medication results in risk reduction. The purpose of this study was to investigate whether nonadherence to medical therapy for cardiovascular morbidity correlates with a higher risk for NAION when compared to patients with strict adherence. Methods: A retrospective case-control study was conducted among members of Clalit Health Services in Israel from 2001 to 2022. For each of the 757 NAION cases, three controls (totaling 2271 patients) were matched based on birth year and sex, with a propensity score analysis employed to adjust for a range of comorbidities. A patient was deemed nonadherent with medical treatment if their purchased quantity of medication was less than 60% of the prescribed annual dosage. Mixed models were used to evaluate exposure differences, and conditional logistic regression was applied, incorporating adjustments for socioeconomic status and ethnicity, to examine the impact of medication nonadherence on NAION risk. Results: A total of 3028 patients were included in the study; 757 patients with the diagnosis of NAION and 2271 in the matched control group. The average age of NAION patients was 69 ± 9 years and 55% were male. After adjustments for socioeconomic status and ethnicity, nonadherence to calcium channel blockers (CCBs) (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.03–1.71) and anti-arrhythmic (OR: 5.67, 95% CI: 1.89–21.2) medications emerged as significant risk factors. Similarly, nonadherence to cardioprotective medications (OR: 1.46, 95% CI: 1.23–1.74) was also identified as a significant risk factor. Conclusions: Nonadherence to treatments for cardiovascular disease, specifically to medications known to improve prognosis, is associated with a higher risk for NAION.