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Choi CJ, Chou JC, Lefebvre DR, Yoon MK. Margin Reflex Distance: Differences Based on Camera and Flash Positions. Ophthal Plast Reconstr Surg 2016;32(3):199-203.Abstract

PURPOSE: To evaluate the effect of camera flash position on the measurement of photographic margin reflex distances (MRD). METHODS: Subjects without any ophthalmic disease were prospectively enrolled after institutional review board approval. Clinical measurements of MRD1 and interpalpebral fissure were obtained. Photographs were then taken with a digital single lens reflex with built-in pop-up flash (dSLR-pop), a dSLR with lens-mounted ring flash (dSLR-ring), a point-and-shoot camera, and a smartphone, each in 4 positions: with the camera upright, rotated 90°, 180°, and 270°. The images were analyzed using ImageJ software to measure MRD1, interpalpebral fissure, horizontal white-to-white, and distance from nasal limbus to the corneal light reflex. RESULTS: Thirty-two eyes of 16 subjects were included (ages 27-65). When using the dSLR-ring, point-and-shoot, and smartphone, the difference between clinical and photographic MRD1 did not reach statistical significance. There was, however, a statistically significant difference in the upright position with dSLR-pop (mean difference 0.703 mm, σ = 0.984 mm, p = 0.0008). For dSLR-pop, photographic MRD1 in upright versus inverted position differed significantly (mean difference -0.562 mm, σ =0.348 mm, p < 0.0001). Photographic MRD1 between dSLR-pop and dSLR-ring showed significant difference in upright position (mean difference -0.572 mm, σ = 0.701 mm, p = 0.0002). There were no statistically significant differences between clinical and photographic interpalpebral fissure, and among white-to-white and nasal limbus to light reflex measurements in any position in all 4 cameras. CONCLUSIONS: When using photographs for measurement of MRD1, cameras with a near-coaxial light source and aperture have values that are most similar to clinical measurements.

Jakobiec FA, Roh M, Stagner AM, Yoon MK. Choristomatous Respiratory Cyst Restricted to the Upper Eyelid. Ophthal Plast Reconstr Surg 2016;32(1):e15-8.Abstract

A 79-year-old man underwent excision of an upper eyelid mass that had been enlarging for 3 months. Histopathologic evaluation demonstrated a cyst lined by pseudostratified columnar epithelium with myriad goblet cells and cilia, and immunostaining revealed cytokeratins indicative of a respiratory origin. This rare condition, the first described exclusively in an eyelid, arises either from a congenital embryologic respiratory epithelial ectopia or the displacement of mature sinus mucosa following trauma or chronic sinus disease. The current case lacked any signs or symptoms of sinus disease or a history of trauma.

Cho H, Pillai P, Nicholson L, Sobrin L. Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring. Ocul Immunol Inflamm 2016;24(2):194-206.Abstract

PURPOSE: To describe the clinical course of uveitis-associated inflammatory papillitis and evaluate the utility and reproducibility of optic nerve spectral domain optical coherence tomography (SD-OCT). METHODS: Data on 22 eyes of 14 patients with uveitis-related papillitis and optic nerve imaging were reviewed. SD-OCT measure reproducibility was determined and parameters were compared in active vs. inactive uveitis. RESULTS: Papillitis resolution lagged behind uveitis resolution in three patients. For SD-OCT measures, the intraclass correlation coefficients were 99.1-100% and 86.9-100% for intraobserver and interobserver reproducibility, respectively. All SD-OCT optic nerve measures except inferior and nasal peripapillary retinal thicknesses were significantly higher in active vs. inactive uveitis after correction for multiple hypotheses testing. Mean optic nerve central thickness decreased from 545.1 to 362.9 µm (p = 0.01). CONCLUSIONS: Resolution of inflammatory papillitis can lag behind resolution of uveitis. SD-OCT assessment of papillitis is reproducible and correlates with presence vs. resolution of uveitis.

Rai R, Yoon MK, Stacy RC. Tick Infestation of the Eyelid With Histopathologic Characterization. Ophthal Plast Reconstr Surg 2016;32(3):e55-8.Abstract

Ocular tick infestation is a rare occurrence. The authors report a case that is unique for being the first published example from New England, for its chronic presentation, and for the inclusion of histopathologic analysis in its diagnostic workup. A 75-year-old man was evaluated for a persistent eyelid growth secondary to an incompletely removed tick that had attached 6 months earlier. The lesion was completely excised, and a partially destroyed arthropod was observed embedded within the tissue. Light microscopy demonstrated a mixed granulomatous reaction. Given the disruption of the tick's anatomy, speciation could not be performed. The patient had an uneventful recovery. A corresponding review of tick bites to the eye is provided.

Campbell AA, Jakobiec FA, Rashid A, Dana R, Yoon MK. Bilateral Sequential Dacryocystitis in a Patient With Graft-Versus-Host Disease. Ophthal Plast Reconstr Surg 2016;32(4):e89-92.Abstract

A 29-year-old woman with a history of 2 bone marrow transplants for acute myelogenous leukemia developed bilateral sequential dacryocystitis in the context of known ocular graft-versus-host disease. With each infection, the patient underwent uneventful dacryocystorhinostomy. Postoperatively, she developed severe dry eye disease requiring replacement of punctal plugs and use of a prosthetic replacement of the ocular surface ecosystem lens. Histopathologic and immunohistochemical examination of the lacrimal sac showed a dense diffuse nonfollicular lymphocytic subepithelial infiltrate in the lacrimal sac that contained moderately more T-cells than B-cells. This is the first report of acute dacryocystitis associated with graft-versus-host disease. The authors caution that similar patients may develop worsening of ocular surface dryness due to restoration of normal lacrimal outflow.

Talcott KE, Lee NG, Freitag SK. Vascular Engorgement of Lacrimal Gland Associated With Port-Wine Stain. Ophthal Plast Reconstr Surg 2016;32(4):e92-4.Abstract

Port-wine stains are congenital dermal capillary malformations that typically involve the head and neck. While most of them are isolated malformations, they have been associated with other vascular findings, including conjunctival, episcleral, and choroidal hemangiomas. They have also been associated with the phakomatosis Sturge-Weber syndrome, characterized by parieto-occipital, leptomeningeal, and ocular choroidal vascular malformations. However, vascular engorgement of the lacrimal gland has not been previously reported in association with port-wine stains. The authors present a case of a 52-year-old man with a long-standing and isolated right periorbital port-wine stain referred for lacrimal gland enlargement on CT scan. He was found to have asymptomatic right lacrimal gland vascular engorgement, which was radiographically stable over a period of 5 years.

Taibbi G, Kim JD, Bakir BH, Shenoy SR, Pearce WA, Taroyan G, Birdsong OC, Loucks EK, Vizzeri G. Correlation and Agreement Between Cirrus HD-OCT "RNFL Thickness Map" and Scan Circle Retinal Nerve Fiber Layer Thickness Measurements. J Glaucoma 2016;25(2):208-16.Abstract

PURPOSE: To evaluate the correlation and agreement between optical coherence tomography (Cirrus HD-OCT) retinal nerve fiber layer (RNFL) thickness map and scan circle RNFL thickness measurements. METHODS: ImageJ and custom Perl scripts were used to derive RNFL thickness measurements from RNFL thickness maps of optic disc scans of healthy and glaucomatous eyes. Average, quadrant, and clock-hour RNFL thickness of the map, and RNFL thickness of the areas inside/outside the scan circle were obtained. Correlation and agreement between RNFL thickness map and scan circle RNFL thickness measurements were evaluated using R and Bland-Altman plots, respectively. RESULTS: A total of 104 scans from 26 healthy eyes and 120 scans from 30 glaucomatous eyes were analyzed. RNFL thickness map and scan circle measurements were highly reproducible (eg, in healthy eyes, average RNFL thickness coefficients of variation were 2.14% and 2.52% for RNFL thickness map and scan circle, respectively) and highly correlated (0.55≤R≤0.98). In general, the scan circle provided greater RNFL thickness than the RNFL thickness map in corresponding sectors and the differences tended to increase as RNFL thickness increased. The width of the 95% limits of agreement ranged between 5.28 and 36.80 μm in healthy eyes, and between 11.69 and 42.89 μm in glaucomatous eyes. CONCLUSIONS: Despite good correlation between RNFL thickness map and scan circle measurements, agreement was generally poor, suggesting that RNFL thickness assessment over the entire scan area may provide additional clinically relevant information to the conventional scan circle analysis. In the absence of available measurements from the entire peripapillary region, the RNFL thickness maps can be used to investigate localized RNFL thinning in areas not intercepted by the scan circle.

Olivares AM, Moreno-Ramos OA, Haider NB. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases. J Exp Neurosci 2015;9(Suppl 2):93-121.Abstract

The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.

Tabebordbar M, Zhu K, Cheng JKW, Chew WL, Widrick JJ, Yan WX, Maesner C, Wu EY, Xiao R, Ran AF, Cong L, Zhang F, Vandenberghe LH, Church GM, Wagers AJ. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 2015;Abstract

Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we develop and test a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored Dystrophin reading frame in myofibers, cardiomyocytes, and muscle stem cells following local or systemic delivery. AAV-Dmd CRISPR-treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle.

Conlin PR, Asefzadeh B, Pasquale LR, Selvin G, Lamkin R, Cavallerano AA. Accuracy of a technology-assisted eye exam in evaluation of referable diabetic retinopathy and concomitant ocular diseases. Br J Ophthalmol 2015;99(12):1622-7.Abstract

BACKGROUND/AIMS: Digital retinal imaging using store-and-forward technology is used to screen for diabetic retinopathy (DR). Its usefulness in detecting non-diabetic eye diseases is uncertain. We determined the level of agreement between teleretinal imaging supplemented with visual acuity and intraocular pressure (IOP) measurements (ie, technology-assisted eye (TAE) exam) and a comprehensive eye exam in evaluation for DR and non-diabetic ocular conditions. METHODS: We conducted a prospective, observational study with two parallel evaluations. Patients with diabetes (n=317) had a TAE exam and a comprehensive eye exam on the same day. A subset of participants with normal baseline exams (n=72) had follow-up exams 1 year later. We measured the level of agreement for referable ocular findings. RESULTS: Agreement for referable ocular findings was moderate (n=389, agreement: 77%; κ: 0.55), due in part to ungradable exams (22%). However, about half of the ungradable exams had findings that warranted referral. There was substantial agreement for follow-up exams (n=72, agreement: 93%; κ: 0.63). Among all gradable exams (n=303), the TAE exam had 86% sensitivity and 84% specificity for referable ocular findings, with high agreement (≥94%) for DR and other major ocular diagnoses. CONCLUSIONS: There was moderate-to-substantial agreement between a TAE exam and a comprehensive eye exam for referable ocular findings in patients with diabetes. Ungradable exams were a frequent marker of ocular pathology. Teleretinal imaging may be a useful evaluation for both diabetic and non-diabetic ocular conditions.

Kundu J, Michaelson A, Talbot K, Baranov P, Young MJ, Carrier RL. Decellularized retinal matrix: natural platforms for human retinal progenitor cell culture. Acta Biomater 2015;Abstract

Tissue decellularization strategies have enabled engineering of scaffolds that preserve native extracellular matrix (ECM) structure and composition. In this study, we developed decellularized retina (decell-retina) thin films. We hypothesized that these films, mimicking the retina niche, would promote human retinal progenitor cell (hRPC) attachment, proliferation and differentiation. Retinas isolated from bovine eyes were decellularized using 1% w/v sodium dodecyl sulfate (SDS) and pepsin digested. The resulting decell-retina was biochemically assayed for composition and cast dried to develop thin films. Attachment, viability, morphology, proliferation and gene expression of hRPC cultured on the films were studied in vitro. Biochemical analyses of decell-retina compared to native retina indicated the bulk of DNA (94%) was removed, while the majority of sulfated GAGs (55%), collagen (83%), hyaluronic acid (87%), and key growth factors were retained. The decell-retina films supported hRPC attachment and growth, with cell number increasing 1.5-fold over a week. RT-PCR analysis revealed hRPC expression of rhodopsin, rod outer membrane, neural retina-specific leucine zipper neural and cone-rod homeobox gene on decell-retina films, indicating photoreceptor development. In conclusion, novel decell-retina films show promise as potential substrates for culture and/or transplantation of retinal progenitor cells to treat retinal degenerative disorders.

Bleier BS, Castelnuovo P, Battaglia P, Turri-Zanoni M, Dallan I, Metson R, Sedaghat AR, Stefko TS, Gardner PA, Snyderman CH, Nogueira JF, Ramakrishnan VR, Muscatello L, Lenzi R, Freitag S. Endoscopic endonasal orbital cavernous hemangioma resection: global experience in techniques and outcomes. Int Forum Allergy Rhinol 2015;Abstract

BACKGROUND: Endoscopic orbital surgery represents the next frontier in endonasal surgery. The current literature is largely composed of small, heterogeneous, case series with little consensus regarding optimal techniques. The purpose of this study was to combine the experience of multiple international centers to create a composite of the global experience on the endoscopic management of a single type of tumor, the orbital cavernous hemangioma (OCH). METHODS: This was a retrospective study of techniques for endoscopic OCH resection from 6 centers on 3 continents. Only primary data from strictly endoscopic resection of OCHs were included. Responses were analyzed to qualitatively identify points of both consensus and variability among the different groups. RESULTS: Data for a total of 23 patients, 10 (43.5%) male and 13 (56.5%) female were collected. The majority of lesions were intraconal (60.9%). The mean ± standard deviation (SD) surgical time was 150.7 ± 75.0 minutes with a mean blood loss of 82.7 ± 49.6 mL. Binarial approaches (26.1%) were used exclusively in the setting of intraconal lesions, which were associated with a higher rate of incomplete resection (31.3%), postoperative diplopia (25.0%), and the need for reconstruction (37.5%) than extraconal lesions. Orthotropia and symmetric orbital appearance were achieved in 60.9% and 78.3% of cases, respectively. CONCLUSION: Extraconal lesions were managed similarly; however, greater variability was evident for intraconal lesions. These included the laterality and number of hands in the approach, methods of medial rectus retraction, and the need for reconstruction. The increased technical complexity and disparity of techniques in addressing intraconal OCHs suggests that continued research into the optimal management of this subclass of lesions is of significant priority.

for the Group WTDCCT/EDICR, Gubitosi-Klug RA, Sun W, Cleary PA, Braffett BH, Aiello LP, Das A, Tamborlane W, Klein R. Effects of Prior Intensive Insulin Therapy and Risk Factors on Patient-Reported Visual Function Outcomes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Cohort. JAMA Ophthalmol 2015;:1-10.Abstract

Importance: Preservation of vision in patients with diabetes mellitus is critical. Interventions to improve glycemic control through early intensive treatment of diabetes reduce rates of severe retinopathy and preserve visual acuity. Objective: To assess the effects of prior intensive insulin treatment and risk factors on patient-reported visual function in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Design, Setting, and Participants: Cohort study of 1184 participants with type 1 diabetes from the DCCT/EDIC study (randomized clinical trial followed by an observational follow-up study) who completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) during EDIC years 17 through 20 (September 1, 2009, through April 30, 2014) in 28 institutions across the United States and Canada. Main Outcomes and Measures: The primary outcome was the composite NEI-VFQ-25 score. Secondary outcomes were visual acuity (measured by the Early Treatment Diabetic Retinopathy Study protocol), retinopathy level (determined by masked grading of stereoscopic color fundus photographs), and NEI-VFQ-25 subscale scores. The composite NEI-VFQ-25 scale and its subscales were scored 0 to 100, corresponding to poor to excellent function, respectively. Results: The overall average NEI-VFQ-25 score for 1184 DCCT/EDIC participants (mean [SD] age, 52.3 [6.9] years; 48% female) with a 30-year duration of diabetes was high (all participants: median, 91.7; interquartile range [IQR], 89.7-96.9; intensive treatment [n = 605]: median, 94.7; IQR, 91.0-97.2; conventional treatment [n = 579]: median, 94.0; IQR, 88.4-96.1; P = .006 for intensive vs conventional). After adjustment for sex, age, hemoglobin A1c level, and retinopathy level at DCCT baseline, the former intensive treatment group had a significant, albeit modest, improvement in overall NEI-VFQ-25 score compared with the former conventional diabetes treatment group (median difference, -1.0; 95% CI, -1.7 to -0.3; P = .006). This beneficial treatment effect was fully attributed to the prior glycemic control in DCCT (explained treatment effect: 100%). Those with visual acuity worse than 20/100 reported the largest decline in visual function (median difference, -21.0; 95% CI, -40.5 to -1.6; P = .03). Conclusions and Relevance: In the DCCT/EDIC cohort, patient-reported visual function remains high in both treatment groups, comparable to previous reports of overall health-related quality of life. Intensive diabetes therapy modestly improved NEI-VFQ-25 score 30 years after the start of the DCCT, the benefit underestimated owing to more nonparticipants from the conventional treatment group. Visual acuity had the greatest effect on patient-reported visual function from among all risk factors. Trial Registration: clinicaltrials.gov Identifiers: NCT00360815 and NCT00360893.

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