Joseph M. Simonett

Early microvascular retinal changes in optical coherence tomography angiography in patients with type 1 diabetes mellitus

Diabetic retinopathy (DR) can lead to significant vision loss and blindness and has a particularly high prevalence in patients with type 1 diabetes (DM1). In this study, we investigate quantitative differences in optical coherence tomography angiography (OCTA) data between DM1 patients with no or mild signs of retinopathy and non‐diabetic subjects.

Macular sub-layer thinning and association with pulmonary function tests in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder that may have anterior visual pathway involvement. In this study, we compare the macular structure of patients with ALS to healthy controls, and examine correlations between macular sub-layer thickness measurements and pulmonary function tests and disease duration. ALS patients underwent optical coherence tomography (OCT) imaging to obtain macular cube scans of the right eye. Macular cube OCT data from age-matched healthy subjects were provided by the OCT reading center. Semi-automated retinal segmentation software was used to quantify macular sub-layers. Pulmonary function tests and time since symptom onset were collected retrospectively from the electronic medical records of ALS patients. Macular retinal nerve fiber layer was significantly thinner in ALS patients compared to healthy controls (P < 0.05). Total macular and other sub-layer thicknesses were not reduced in the ALS cohort. Macular retinal nerve fiber layer thickness positively correlated with forced vital capacity % predicted and forced expiratory volume in 1 second % predicted (P < 0.05). In conclusion, analysis of OCT measurements supports the involvement of the anterior visual pathway in ALS. Subtle structural thinning in the macular retinal nerve fiber layer correlates with pulmonary function tests.

Clinicopathologic report of ocular involvement in ALS patients with C9orf72 mutation.

Abstract Our objective was to present clinicopathologic evidence of anterior visual pathway involvement in patients with amyotrophic lateral sclerosis (ALS) secondary to a C9orf72 mutation. Two related patients from an extended pedigree with ALS and GGGGCC hexanucleotide repeat expansion in the C9orf72 gene (C9-ALS) underwent neuro-ophthalmologic examination. Following death and tissue donation of the younger ALS patient, histopathologic examination of the retina, optic nerve and central nervous system (CNS) was performed. Ophthalmologic examination revealed contrast sensitivity impairment in the younger C9-ALS patient. Immunohistochemistry performed on this patient’s donor tissue demonstrated p62-positive, pTDP43-negative perinuclear inclusions in the inner nuclear layer of the retina and CNS. Further colocalization with GLT-1 and recoverin suggested that the majority of retinal p62-positive inclusions are found within cone bipolar cells as well as some amacrine and horizontal cells. In conclusion, this is the first report that identifies disease-specific pathologic inclusions in the anterior visual pathway of a patient with a C9orf72 mutation. Cone bipolar cell involvement within the inner nuclear layer of the retina may explain the observed subtle visual function deficiencies in this patient. Further clinical and histopathologic studies are needed to fully characterize a larger population of C9-ALS patients and explore these findings in other forms of ALS.

Retinal nerve fiber layer thickness in amnestic mild cognitive impairment: Case-control study and meta-analysis.

Retinal structural changes in subjects with mild cognitive impairment (MCI) remain a subject of controversy.

LONGITUDINAL QUANTITATIVE EVALUATION OF PHOTORECEPTOR VOLUME FOLLOWING REPAIR OF MACULA-OFF RETINAL DETACHMENT.

Purpose: To quantify photoreceptor volume changes after successful surgical repair of macula-off retinal detachment and to correlate these volumetric changes to postoperative best-corrected visual acuity (BCVA). Methods: Retrospective study of 15 eyes of 15 patients with macula-off retinal detachment who underwent successful surgical repair. A minimum of 4 optical coherence tomography scans that straddled the foveal center was used to quantify the central photoreceptor volume (central 1 mm). Results: Mean photoreceptor volume at the first postoperative visit was 0.451 mm3, increasing to 0.523 mm3 at the final postoperative visit (P = 0.004). Mean BCVA improved from 1.13 ± 0.59 logarithm of the minimum angle of resolution units (∼20/270) preoperatively to 0.52 ± 0.42 logarithm of the minimum angle of resolution units (∼20/66) at the final postoperative visit (P = 0.001). Mean photoreceptor volume at either the initial or final visit demonstrated significant correlations with final postoperative BCVA (r = −0.670, P = 0.017 and r = −0.753, P = 0.005, respectively). Shorter time interval from diagnosis to surgery was significantly associated with greater mean final postoperative photoreceptor volume (r = −0.588, P = 0.021) and better mean final postoperative BCVA (r = 0.709, P = 0.003). Conclusion: We observed a significant increase in photoreceptor volume after successful retinal detachment repair; photoreceptor volume was positively associated with BCVA and time to surgery. Our series emphasizes the importance of prompt surgical repair and shows that photoreceptor recovery and volumetric improvement correlate significantly with BCVA.

LONGITUDINAL QUANTITATIVE EVALUATION OF OUTER RETINAL LESIONS IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY USING OPTICAL COHERENCE TOMOGRAPHY.

Purpose: To quantify the external limiting membrane (ELM) disruption and photoreceptor volume changes in eyes with acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using Spectral Domain Optical Coherence Tomography (SD-OCT) at the acute and resolution phases. Methods: Retrospective study of 10 eyes of 5 patients with APMPPE. Intact ELM and the Bruchs membrane were manually traced using ImageJ software and their lengths from each scan of the Spectral Domain Optical Coherence Tomography macular volume were summed. The ratio of intact ELM length/Bruchs membrane length was calculated. Also, two-dimensional areas of specific regions of interest were demarcated between the intact ELM and Bruchs Membrane in every cross-sectional B-scan. Total volume of photoreceptors was calculated by multiplying the total area by the distance between B-scans. Results: There was a statistically significant increase in ELM/Bruchs membrane ratio (P value = 0.022), mean photoreceptors volume (P value = 0.028), and a significant linear positive correlation between change of intact ELM/Bruchs membrane ratio and percent change of photoreceptor volume (r = 0.927, P value = 0.001) when comparing baseline and final follow-up visit, independent of total follow-up length. Conclusion: Using Spectral Domain-Optical Coherence Tomography, we showed that quantitative evaluation of ELM disruption and the volume of photoreceptor recovery can help us to follow the clinical course of APMPPE.

A validated phenotyping algorithm for genetic association studies in age-related macular degeneration

Age-related macular degeneration (AMD), a multifactorial, neurodegenerative disease, is a leading cause of vision loss. With the rapid advancement of DNA sequencing technologies, many AMD-associated genetic polymorphisms have been identified. Currently, the most time consuming steps of these studies are patient recruitment and phenotyping. In this study, we describe the development of an automated algorithm to identify neovascular (wet) AMD, non-neovascular (dry) AMD and control subjects using electronic medical record (EMR)-based criteria. Positive predictive value (91.7%) and negative predictive value (97.5%) were calculated using expert chart review as the gold standard to assess algorithm performance. We applied the algorithm to an EMR-linked DNA bio-repository to study previously identified AMD-associated single nucleotide polymorphisms (SNPs), using case/control status determined by the algorithm. Risk alleles of three SNPs, rs1061170 (CFH), rs1410996 (CFH), and rs10490924 (ARMS2) were found to be significantly associated with the AMD case/control status as defined by the algorithm. With the rapid growth of EMR-linked DNA biorepositories, patient selection algorithms can greatly increase the efficiency of genetic association study. We have found that stepwise validation of such an algorithm can result in reliable cohort selection and, when coupled within an EMR-linked DNA biorepository, replicates previously published AMD-associated SNPs.

Longitudinal Microperimetry Evaluation After Intravitreal Ocriplasmin Injection For Vitreomacular Traction

Purpose: To determine whether improvements in microperimetry testing are associated with anatomic resolution after ocriplasmin treatment in patients with symptomatic vitreomacular adhesion (VMA)/vitreomacular traction and relatively preserved baseline best-corrected visual acuity (BCVA). Methods: Patients with vitreomacular traction received a single 125-&mgr;g intravitreal ocriplasmin injection and were followed longitudinally for 6 months with optical coherence tomography, BCVA testing, and microperimetry. Visual function changes were compared between eyes with and without VMA resolution on optical coherence tomography. Results: Eleven of 16 eyes (68.8%) achieved VMA resolution after treatment. Mean baseline BCVA was relatively good (79 ± 3 Early Treatment Diabetic Retinopathy Study letters; 20/52); no patients had a ≥2-line improvement in BCVA over the 6-month follow-up period. In the group with VMA resolution, mean retinal sensitivity significantly increased in the central 4° (15.2 ± 1.9 dB vs. 18.9 ± 0.7 dB, P < 0.001) when comparing baseline and final follow-up microperimetry testing. No change in mean retinal sensitivity was found in the group without VMA resolution. Conclusion: Microperimetry demonstrates a significant gain in retinal sensitivity, particularly in the central 4° area, in eyes with anatomic resolution after treatment of vitreomacular traction with intravitreal ocriplasmin injection, even when no significant gain in BCVA is seen.

Quantitative Analysis of En Face Spectral-Domain Optical Coherence Tomography Imaging in Polypoidal Choroidal Vasculopathy

BACKGROUND AND OBJECTIVE Spectral-domain optical coherence tomography (SD-OCT) imaging can be used to visualize polypoidal choroidal vasculopathy (PCV) lesions in the en face plane. Here, the authors describe a novel lesion quantification technique and compare PCV lesion area measurements and morphology before and after anti-vascular endothelial growth factor (VEGF) treatment. PATIENTS AND METHODS Volumetric SD-OCT scans in eyes with PCV before and after induction anti-VEGF therapy were retrospectively analyzed. En face SD-OCT images were generated and a pixel intensity thresholding process was used to quantify total lesion area. RESULTS Thirteen eyes with PCV were analyzed. En face SD-OCT PCV lesion area quantification showed good intergrader reliability (intraclass correlation coefficient = 0.944). Total PCV lesion area was significantly reduced after anti-VEGF therapy (2.22 mm2 vs. 2.73 mm2; P = .02). The overall geographic pattern of the branching vascular network was typically preserved. CONCLUSION PCV lesion area analysis using en face SD-OCT is a reproducible tool that can quantify treatment related changes. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:126-133.].