Alström's Syndrome, Leber's Hereditary Optic Neuropathy, or Retinitis Pigmentosa? A Case of Misdiagnosis.

A case of a patient with the Alström syndrome (AS) that was misdiagnosed as Leber's hereditary optic neuropathy or retinitis pigmentosa for 13 years is presented. AS is a rare genetic disorder caused by mutations in the ALMS1 gene. AS may lead to abnormal ciliary formation and function. AS affects metabolism, and symptomatology includes type 2 diabetes mellitus (T2DM), obesity, hypogonadism and gynecomastia in males, progressive bilateral sensorineural hearing loss, cardiomyopathy, nonalcoholic fatty liver disease (NAFLD), cirrhosis, and chronic progressive kidney disease. The onset of the above symptoms may vary significantly. The ophthalmic manifestation is early onset cone-rod dystrophy that starts as progressive vision loss, photophobia, and nystagmus in the first months of life. An accurate diagnosis may enable specialists to facilitate a significantly positive effect in the everyday life of a patient. Genetic counseling may also be recommended for these patients. Diagnosis was confirmed by DNA testing, thus highlighting its necessity in everyday practice.

Age-Related Differences in Ocular Features of a Naturalistic Free-Ranging Population of Rhesus Macaques.

Purpose: Rhesus macaques (Macaca mulatta) are the premier nonhuman primate model for studying human health and disease. We investigated if age was associated with clinically relevant ocular features in a large cohort of free-ranging rhesus macaques from Cayo Santiago, Puerto Rico. Methods: We evaluated 120 rhesus macaques (73 males, 47 females) from 0 to 29 years old (mean ± SD: 12.6 ± 6.4) from September to December 2021. The ophthalmic evaluation included intraocular pressure (IOP) assessment, corneal pachymetry, biomicroscopy, A-scan biometry, automated refraction, and fundus photography after pupil dilation. The associations of age with the outcomes were investigated through multilevel mixed-effects models adjusted for sex and weight. Results: On average, IOP, pachymetry, axial length, and automated refraction spherical equivalent were 18.37 ± 4.68 mmHg, 474.43 ± 32.21 µm, 19.49 ± 1.24 mm, and 0.30 ± 1.70 diopters (D), respectively. Age was significantly associated with pachymetry (ß coefficient = -1.20; 95% confidence interval [CI], -2.27 to -0.14; P = 0.026), axial length (ß coefficient = 0.03; 95% CI, 0.01 to 0.05; P = 0.002), and spherical equivalent (ß coefficient = -0.12; 95% CI, -0.22 to -0.02; P = 0.015). No association was detected between age and IOP. The prevalence of cataracts in either eye was 10.83% (95% CI, 6.34-17.89) and was significantly associated with age (odds ratio [OR] = 1.20; 95% CI, 1.06-1.36; P = 0.004). Retinal drusen in either eye was observed in 15.00% (95% CI, 9.60-22.68) of animals, which was also significantly associated with age (OR = 1.14; 95% CI, 1.02-1.27; P = 0.020). Conclusions: Rhesus macaques exhibit age-related ocular associations similar to those observed in human aging, including decreased corneal thickness, increased axial length, myopic shift, and higher prevalence of cataract and retinal drusen.

Under Pressure: Lamina Cribrosa Pore Path Tortuosity in Response to Acute Pressure Modulation.

Purpose: Lamina cribrosa (LC) deformation is hypothesized to play a major role in glaucoma pathogenesis. The purpose of this study was to determine in vivo how varying intraocular pressure (IOP) under fixed intracranial pressure (ICP), and vice versa, deforms the pore paths throughout the LC volume. Methods: Spectral-domain optical coherence tomography scans of the optic nerve head were acquired from healthy adult rhesus monkeys under different pressures. IOP and ICP were controlled with gravity-based perfusion systems into the anterior chamber and lateral ventricle, respectively. IOP and ICP were modulated from baseline to high (19-30 mmHg) and highest (35-50 mmHg) levels while maintaining a fixed ICP of 8 to 12 mmHg and IOP of 15 mmHg, respectively. After three-dimensional registration and segmentation, the paths of pores visible in all settings were tracked based on their geometric centroids. Pore path tortuosity was defined as the measured distance divided by the minimal distance between the most anterior and posterior centroids. Results: The median pore tortuosity at baseline varied among the eyes (range, 1.16-1.68). For the IOP effect under fixed ICP (six eyes, five animals), two eyes showed statistically significant increased tortuosity and one showed a decrease (P < 0.05, mixed-effects model). No significant change was detected in three eyes. When modulating ICP under fixed IOP (five eyes, four animals), a similar response pattern was detected. Conclusions: Baseline pore tortuosity and the response to acute pressure increase vary substantially across eyes. Translational Relevance: LC pore path tortuosity could be associated with glaucoma susceptibility.

The Development and Clinical Application of Innovative Optical Ophthalmic Imaging Techniques.

The field of ophthalmic imaging has grown substantially over the last years. Massive improvements in image processing and computer hardware have allowed the emergence of multiple imaging techniques of the eye that can transform patient care. The purpose of this review is to describe the most recent advances in eye imaging and explain how new technologies and imaging methods can be utilized in a clinical setting. The introduction of optical coherence tomography (OCT) was a revolution in eye imaging and has since become the standard of care for a plethora of conditions. Its most recent iterations, OCT angiography, and visible light OCT, as well as imaging modalities, such as fluorescent lifetime imaging ophthalmoscopy, would allow a more thorough evaluation of patients and provide additional information on disease processes. Toward that goal, the application of adaptive optics (AO) and full-field scanning to a variety of eye imaging techniques has further allowed the histologic study of single cells in the retina and anterior segment. Toward the goal of remote eye care and more accessible eye imaging, methods such as handheld OCT devices and imaging through smartphones, have emerged. Finally, incorporating artificial intelligence (AI) in eye images has the potential to become a new milestone for eye imaging while also contributing in social aspects of eye care.

Microstructural Deformations Within the Depth of the Lamina Cribrosa in Response to Acute In Vivo Intraocular Pressure Modulation.

Purpose: The lamina cribrosa (LC) is a leading target for initial glaucomatous damage. We investigated the in vivo microstructural deformation within the LC volume in response to acute IOP modulation while maintaining fixed intracranial pressure (ICP). Methods: In vivo optic nerve head (ONH) spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) were obtained from eight eyes of healthy adult rhesus macaques (7 animals; ages = 7.9-14.4 years) in different IOP settings and fixed ICP (8-12 mm Hg). IOP and ICP were controlled by cannulation of the anterior chamber and the lateral ventricle of the brain, respectively, connected to a gravity-controlled reservoir. ONH images were acquired at baseline IOP, 30 mm Hg (H1-IOP), and 40 to 50 mm Hg (H2-IOP). Scans were registered in 3D, and LC microstructure measurements were obtained from shared regions and depths. Results: Only half of the eyes exhibited LC beam-to-pore ratio (BPR) and microstructure deformations. The maximal BPR change location within the LC volume varied between eyes. BPR deformer eyes had a significantly higher baseline connective tissue volume fraction (CTVF) and lower pore aspect ratio (P = 0.03 and P = 0.04, respectively) compared to BPR non-deformer. In all eyes, the magnitude of BPR changes in the anterior surface was significantly different (either larger or smaller) from the maximal change within the LC (H1-IOP: P = 0.02 and H2-IOP: P = 0.004). Conclusions: The LC deforms unevenly throughout its depth in response to IOP modulation at fixed ICP. Therefore, analysis of merely the anterior LC surface microstructure will not fully capture the microstructure deformations within the LC. BPR deformer eyes have higher CTVF than BPR non-deformer eyes.

3D Microstructure of the Healthy Non-Human Primate Lamina Cribrosa by Optical Coherence Tomography Imaging.

Purpose: The lamina cribrosa (LC) has an important role in the pathophysiology of ocular diseases. The purpose of this study is to characterize in vivo, noninvasively, and in 3D the structure of the LC in healthy non-human primates (NHPs). Methods: Spectral-domain optical coherence tomography (OCT; Leica, Chicago, IL) scans of the optic nerve head (ONH) were obtained from healthy adult rhesus macaques monkeys. Using a previously reported semi-automated segmentation algorithm, microstructure measurements were assessed in central and peripheral regions of an equal area, in quadrants and depth-wise. Linear mixed-effects models were used to compare parameters among regions, adjusting for visibility, age, analyzable depth, graded scan quality, disc area, and the correlation between eyes. Spearmen's rank correlation coefficients were calculated for assessing the association between the lamina's parameters. Results: Sixteen eyes of 10 animals (7 males and 3 females; 9 OD, 7 OS) were analyzed with a mean age of 10.5 ± 2.1 years. The mean analyzable depth was 175 ± 37 µm, with average LC visibility of 25.4 ± 13.0% and average disc area of 2.67 ± 0.45mm2. Within this volume, an average of 74.9 ± 39.0 pores per eye were analyzed. The central region showed statistically significantly thicker beams than the periphery. The quadrant-based analysis showed significant differences between the superior and inferior quadrants. The anterior LC had smaller beams and pores than both middle and posterior lamina. Conclusions: Our study provides in vivo microstructure details of NHP's LC to be used as the foundation for future studies. We demonstrated mostly small but statistically significant regional variations in LC microstructure that should be considered when comparing LC measurements.

Secondary DMEK following failed primary DMEK.

PURPOSE: To report the outcomes of secondary Descemet Membrane Endothelial Keratoplasty (DMEK) performed for failed primary DMEK. METHODS: The medical records of all patients undergoing secondary DMEK due to failure of primary DMEK were reviewed. Reasons for failure were sought and best-corrected visual acuity (BCVA), endothelial cell density (ECD) and complications of secondary DMEK were evaluated. RESULTS: A total of 10 cases undergoing secondary DMEK following failed primary DMEK were identified. Presumed reasons for failure included donor ECD ≤ 2300 cells/mm2 (n = 4), difficulty during graft preparation (n = 2), graft detachment (n = 2), acute angle closure due to retroiridal air dislocation (n = 1), inverse graft positioning (n = 1) and phacoemulsification (n = 1). Eyes with low visual potential were not excluded from the study group. We should note that one patient (case no7) had both low ECD and graft detachment as reasons for failure and as a result he is counted twice. Median BCVA (decimal fraction) increased from 0.1 (range, 0.01; 0.3) to 0.5 (0.05; 1.0) at one month and remained stable thereafter. A BCVA of 0.5 or higher was achieved in 7 cases at the final follow-up. Mean ECD fell from 2628 ± 284 cells/mm2 to 1391 ± 252cells/mm2 at 6 months (47% reduction) and 959 ± 225cells/mm2 at 24 months (64% reduction) (P ≤ 0.028). Complications included the incomplete removal of the primary graft and mild iris bleeding, decompensation of a preexisting primary open-angle glaucoma and retroiridal air dislocation. CONCLUSIONS: Apart from low donor ECD, surgical challenges, i.e., difficulty with graft preparation, inverse graft positioning, and retroiridal air dislocation, were main reasons for failure of primary DMEK. Secondary DMEK showed a good safety profile and reasonable visual outcomes.