Thrombospondin Mutations and Patients With Primary Congenital Glaucoma in a United States Population.

Mutations in the thrombospondin 1 ( THBS1 ) gene have been previously reported in primary congenital glaucoma (PCG) pedigrees that exhibit autosomal dominant inheritance with low penetrance. We sought to determine the role of THBS1 mutations in a cohort of 20 patients with PCG and 362 normal controls from Iowa using a combination of Sanger sequencing and whole exome sequencing. We detected 16 different THBS1 variants, including 4 rare, nonsynonymous variants (p.Thr611Met, p.Asn708Lys, p.Gln1089His, and p.Glu1166Lys). However, none of these variants were judged to be disease-causing mutations based on: 1) prevalence in cases and controls from Iowa, 2) prevalence in the public database gnomAD, 3) mutation analysis algorithms, and 4) THBS1 DNA sequence conservation. These results indicate THBS1 mutations are not a common cause of PCG in patients from Iowa and may be a rare cause of PCG overall.

Exome-based investigation of the genetic basis of human pigmentary glaucoma.

BACKGROUND: Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. RESULTS: Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. CONCLUSIONS: We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.

Nanophthalmos patient with a THR518MET mutation in MYRF, a case report.

BACKGROUND: Nanophthalmos has a significant genetic background and disease-causing mutations have been recently been reported in the myelin regulatory factor (MYRF) gene. We report clinical features in a patient with nanophthalmos and a Thr518Met MYRF mutation. CASE PRESENTATION: A three-year-old male was discovered to have nanophthalmos after first presenting to the emergency department for a frontal headache, eye pain, emesis, and lethargy. Imaging studies (CT and MRI) were negative except for increased posterior fossa cerebrospinal fluid. Subsequent examinations revealed nanophthalmos (short axial eye lengths 18.1 mm OD and 18.3 mm OS), microcornea, and a large crystalline lens. Peripheral chorioretinal pigment abnormalities were also observed. He experienced episodes of marked ocular hypertension (53 mmHg OD and 60 mmHg) likely due to intermittent angle closure precipitated by nanophthalmos. The ocular hypertension was responsive to topical medicines. Genetic analysis of known nanophthalmos genes MFRP and TMEM98 were negative, while a novel mutation, Thr518Met was detected in MYRF. The Thr518Met mutation was absent from 362 matched normal controls and was extremely rare in a large population database, allele frequency of 0.000024. The Thr518Met mutation altered a highly conserved amino acid in the MYRF protein and three of four algorithms suggested that this mutation is likely pathogenic. Finally, molecular modeling showed that the Thr518Met mutation is damaging to MYRF structure. Together these data suggest that the Thr518Met mutation causes nanophthalmos. CONCLUSIONS: Nanophthalmos may present at an early age with features of angle closure glaucoma and a Thr518Met mutation in MYRF was detected in a patient with nanophthalmos. Prevalence data, homology data, mutation analysis data, and protein modeling data suggest that this variant is pathogenic and may expand the phenotypic range of syndromic nanophthalmos caused by MYRF mutations to include central nervous system abnormalities (increased posterior fossa cerebrospinal fluid).

Room-Temperature Ferromagnetic Ultrathin α-MoO3:Te Nanoflakes.

We materialized room-temperature ferromagnetism in ultrathin α-MoO3:Te nanoflakes. The α-MoO3:Te nanoflakes, which had been grown by vapor-phase epitaxy, clearly exhibited an Ag Raman band from symmetric stretching of υ(Mo-O3-Mo) in the 2D-like ultrathin α-MoO3:Te layer. Due to the intentional incorporation of smaller Te ions into bigger Mo sites, the pentacoordinated Mo5+ bonds were created inside the orthorhombic α-MoO3:Te lattice system. Since Mo5+ ions have magnetic moments from unpaired electron spins, a large number of overlapped bound magnetic polarons could be formed via ferromagnetic coupling with charged oxygen vacancies that are inevitably generated at pentacoordinated [Mo5+O5] centers. This gives rise to the increase in long-range ferromagnetic ordering and leads to room-temperature ferromagnetism in the entire α-MoO3:Te solid-state system. The results may move a step closer to the demonstration of spin functionalities in the wide bandgap semiconductor α-MoO3:Te.

Choriocapillaris Degeneration in Geographic Atrophy.

Early age-related macular degeneration (AMD) is characterized by degeneration of the choriocapillaris, the vascular supply of retinal photoreceptor cells. We assessed vascular loss during disease progression in the choriocapillaris and larger vessels in the deeper choroid. Human donor maculae from controls (n = 99), early AMD (n = 35), or clinically diagnosed with geographic atrophy (GA; n = 9, collected from outside the zone of retinal pigment epithelium degeneration) were evaluated using Ulex europaeus agglutinin-I labeling to discriminate between vessels with intact endothelial cells and ghost vessels. Morphometric analyses of choriocapillaris density (cross-sectional area of capillary lumens divided by length) and of vascular lumen/stroma ratio in the outer choroid were performed. Choriocapillaris loss was observed in early AMD (Bonferroni-corrected P = 0.024) with greater loss in GA (Bonferroni-corrected P < 10-9), even in areas of intact retinal pigment epithelium. In contrast, changes in lumen/stroma ratio in the outer choroid were not found to differ between controls and AMD or GA eyes (P > 0.05), suggesting choriocapillaris changes are more prevalent in AMD than those in the outer choroid. In addition, vascular endothelial growth factor-A levels were negatively correlated with choriocapillaris vascular density. These findings support the concept that choroidal vascular degeneration, predominantly in the microvasculature, contributes to dry AMD progression. Addressing capillary loss in AMD remains an important translational target.

Myocilin Mutations in Patients With Normal-Tension Glaucoma.

Importance: Mutations in the myocilin (MYOC) gene are the most common molecularly defined cause of primary open-angle glaucoma that typically occurs in patients with high intraocular pressures (IOP). One MYOC mutation, p.Gln368Ter, has been associated with as many as 1.6% of primary open-angle glaucoma cases that had a mean maximum recorded IOP of 30 mm Hg. However, to our knowledge, the role of the p.Gln368Ter mutation in patients with normal-tension glaucoma (NTG) with an IOP of 21 mm Hg or lower has not been investigated. Objective: To evaluate the role of the p.Gln368Ter MYOC mutation in patients with NTG. Design, Setting, and Participants: In this case-control study of the prevalence of the p.Gln368Ter mutation in patients with NTG, cohort 1 was composed of 772 patients with NTG and 2152 controls from the United States (Iowa, Minnesota, and New York) and England and cohort 2 was composed of 561 patients with NTG and 2606 controls from the Massachusetts Eye and Ear Infirmary and the NEIGHBORHOOD consortium. Genotyping was conducted using real-time polymerase chain reaction that was confirmed with Sanger sequencing, the imputation of genome-wide association study data, or an analysis of whole-exome sequence data. Data analysis occurred between April 2007 and April 2018. Main Outcomes and Measures: Comparison of the frequency of the p.Gln368Ter MYOC mutation between NTG cases and controls with the Fisher exact test. Results: Of 6091 total participants, 3346 (54.9%) were women and 5799 (95.2%) were white. We detected the p.Gln368Ter mutation in 7 of 772 patients with NTG (0.91%) and 7 of 2152 controls (0.33%) in cohort 1 (P = .03). In cohort 2, we detected the p.Gln368Ter mutation in 4 of 561 patients with NTG (0.71%) and 10 of 2606 controls (0.38%; P = .15). When the cohorts were analyzed as a group, the p.Gln368Ter mutation was associated with NTG (odds ratio, 2.3; 95% CI, 0.98-5.3; P = .04). Conclusions and Relevance: In cohorts 1 and 2, the p.Gln368Ter mutation in MYOC was found in patients with IOPs that were 21 mm Hg or lower (NTG), although at a frequency that is lower than previously detected in patients with higher IOP. These data suggest that the p.Gln368Ter mutation may be associated with glaucoma in patients with normal IOPs as well as in patients with IOPs that are greater than 21 mm Hg.

The Heritability of Pigment Dispersion Syndrome and Pigmentary Glaucoma.

PURPOSE: Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are presumed to be inherited in an autosomal dominant manner. We examine relatives of patients with PDS and PG in order to determine the heritability of these diseases. DESIGN: This was a prospective, cross-sectional study. METHODS: One hundred and one patients with PDS were prospectively recruited over 11 months. Four of the patients had PDS without ocular hypertension or glaucoma, 6 had PDS and ocular hypertension, and 91 had PG. Criteria for PDS were 2 of 3 signs: Krukenberg spindle, midperipheral iris transillumination defects, and/or heavy trabecular meshwork pigmentation. Criteria for PG were PDS and 2 of 3 signs: intraocular pressure >21 mm Hg, glaucomatous optic nerve damage, and/or glaucomatous visual field loss. Ninety-nine first-degree relatives living within a 100-mile radius of Iowa City, Iowa were examined in the clinic to determine the probability of familial transmission. RESULTS: A total of 10 of 99 (10.10%) first-degree relatives were diagnosed with PDS (1 with PDS alone, 2 with PDS and ocular hypertension, and 7 with PG). Seven families with ≥2 affected members were identified. The majority of affected family members (8/10) showed moderate to heavy trabecular meshwork pigmentation and either Krukenberg spindle or transillumination defects. CONCLUSIONS: Most of the cases of PDS in our study were sporadic, and the risk to first-degree relatives is lower than previously reported. However, there are families with apparent autosomal dominant inheritance of PDS in which the risk to relatives may be high.

Excessive Daytime Sleepiness and Injury of the Ascending Reticular Activating System Following Whiplash Injury.

Objectives: This study investigated injuries of the ascending reticular activating system (ARAS) following whiplash injury, in patients with excessive daytime sleepiness (EDS). Methods: Twenty-three patients with whiplash injury and 26 healthy control subjects were recruited for this study. Epworth Sleepiness Scale (ESS) was used for evaluating sleepiness. According to the ESS score, the patients were classified into two groups: subgroup A - ESS score <10, and subgroup B - ESS score ≥10. Three components of the ARAS (lower dorsal, lower ventral, and upper) were evaluated for fractional anisotropy (FA) and tract volume (TV). Results: No significant differences were observed in the FA and TV values of the lower dorsal and upper ARAS between the patient and control groups (p > 0.05). Conversely, the values of FA and TV in the lower ventral ARAS of the patient group were significantly lower than those of the control group (p < 0.05). Comparing the values of subgroups A and B, the TV value of subgroup B was significantly lower than subgroup A (p < 0.05). However, no significant differences were observed in the values of the FA and TV in the lower dorsal and upper ARAS, and the FA value in the lower ventral ARAS (p > 0.05). Conclusions: We found significant injury of the lower ventral ARAS in EDS patients with whiplash injury. These results suggest that diffusion tensor tractography (DTT) could provide useful information for detecting injuries of the ARAS following whiplash injury, in patients with EDS.

Glaucoma-associated corneal endothelial cell damage: A review.

The corneal endothelium is critical in maintaining a healthy and clear cornea. Corneal endothelial cells have a significant reserve function, but preservation of these cells is paramount as they have limited regenerative capacity. Glaucoma is a prevalent disease, and damage to the corneal endothelium may be caused by the disease process itself as well as by its treatment. The mechanisms involved in glaucoma-associated damage to the corneal endothelium need further investigation. Understanding how glaucoma and glaucoma surgery impact the endothelium is important for protecting corneal clarity and visual acuity in all glaucoma patients, including those undergoing corneal transplant. We will discuss a range of identified factors that may impact corneal endothelial cell health in glaucoma, including intraocular pressure, glaucoma medications, surgical glaucoma management, mechanical forces, and alterations in the aqueous environment.

Genomic Organization of TBK1 Copy Number Variations in Glaucoma Patients.

BACKGROUND: Approximately 1% of normal tension glaucoma (NTG) cases are caused by TANK-binding kinase 1 (TBK1) gene duplications and triplications. However, the precise borders and orientation of these TBK1 gene copy number variations (CNVs) on chromosome 12 are unknown. METHODS: We determined the exact borders of TBK1 CNVs and the orientation of duplicated or triplicated DNA segments in 5 NTG patients with different TBK1 mutations using whole-genome sequencing. RESULTS: Tandemly duplicated chromosome segments spanning the TBK1 gene were detected in 4 NTG patients, each with unique borders. Four of 5 CNVs had borders located within interspersed repetitive DNA sequences (Alu and long interspersed nuclear element-L1 elements), suggesting that mismatched homologous recombinations likely generated these CNVs. A fifth NTG patient had a complex rearrangement including triplication of a chromosome segment spanning the TBK1 gene. CONCLUSIONS: No specific mutation hotspots for TBK1 CNVs were detected, however, interspersed repetitive sequences (ie, Alu elements) were identified at the borders of TBK1 CNVs, which suggest that mismatch of these elements during meiosis may be the mechanism that generated TBK1 gene dosage mutations.

Optical Coherence Tomography Analysis Based Prediction of Humphrey 24-2 Visual Field Thresholds in Patients With Glaucoma.

Purpose: A pilot study showed that prediction of individual Humphrey 24-2 visual field (HVF 24-2) sensitivity thresholds from optical coherence tomography (OCT) image analysis is possible. We evaluate performance of an improved approach as well as 3 other predictive algorithms on a new, fully independent set of glaucoma subjects. Methods: Subjects underwent HVF 24-2 and 9-field OCT (Heidelberg Spectralis) testing. Nerve fiber (NFL), and ganglion cell and inner plexiform (GCL+IPL) layers were cosegmented and partitioned into 52 sectors matching HVF 24-2 test locations. The Wilcoxon rank sum test was applied to test correlation R, root mean square error (RMSE), and limits of agreement (LoA) between actual and predicted thresholds for four prediction models. The training data consisted of the 9-field OCT and HVF 24-2 thresholds of 111 glaucoma patients from our pilot study. Results: We studied 112 subjects (112 eyes) with early, moderate, or advanced primary and secondary open angle glaucoma. Subjects with less than 9 scans (15/112) or insufficient quality segmentations (11/97) were excluded. Retinal ganglion cell axonal complex (RGC-AC) optimized had superior average R = 0.74 (95% confidence interval [CI], 0.67-0.76) and RMSE = 5.42 (95% CI, 5.1-5.7) dB, which was significantly better (P < 0.05/3) than the other three models: Naïve (R = 0.49; 95% CI, 0.44-0.54; RMSE = 7.24 dB; 95% CI, 6.6-7.8 dB), Garway-Heath (R = 0.66; 95% CI, 0.60-0.68; RMSE = 6.07 dB; 95% CI, 5.7-6.5 dB), and Donut (R = 0.67; 95% CI, 0.61-0.69; RMSE = 6.08 dB, 95% CI, 5.8-6.4 dB). Conclusions: The proposed RGC-AC optimized predictive algorithm based on 9-field OCT image analysis and the RGC-AC concept is superior to previous methods and its performance is close to the reproducibility of HVF 24-2.

A machine-learning graph-based approach for 3D segmentation of Bruch's membrane opening from glaucomatous SD-OCT volumes.

Bruch's membrane opening-minimum rim width (BMO-MRW) is a recently proposed structural parameter which estimates the remaining nerve fiber bundles in the retina and is superior to other conventional structural parameters for diagnosing glaucoma. Measuring this structural parameter requires identification of BMO locations within spectral domain-optical coherence tomography (SD-OCT) volumes. While most automated approaches for segmentation of the BMO either segment the 2D projection of BMO points or identify BMO points in individual B-scans, in this work, we propose a machine-learning graph-based approach for true 3D segmentation of BMO from glaucomatous SD-OCT volumes. The problem is formulated as an optimization problem for finding a 3D path within the SD-OCT volume. In particular, the SD-OCT volumes are transferred to the radial domain where the closed loop BMO points in the original volume form a path within the radial volume. The estimated location of BMO points in 3D are identified by finding the projected location of BMO points using a graph-theoretic approach and mapping the projected locations onto the Bruch's membrane (BM) surface. Dynamic programming is employed in order to find the 3D BMO locations as the minimum-cost path within the volume. In order to compute the cost function needed for finding the minimum-cost path, a random forest classifier is utilized to learn a BMO model, obtained by extracting intensity features from the volumes in the training set, and computing the required 3D cost function. The proposed method is tested on 44 glaucoma patients and evaluated using manual delineations. Results show that the proposed method successfully identifies the 3D BMO locations and has significantly smaller errors compared to the existing 3D BMO identification approaches.

Incorporation of gradient vector flow field in a multimodal graph-theoretic approach for segmenting the internal limiting membrane from glaucomatous optic nerve head-centered SD-OCT volumes.

The internal limiting membrane (ILM) separates the retina and optic nerve head (ONH) from the vitreous. In the optical coherence tomography volumes of glaucoma patients, while current approaches for the segmentation of the ILM in the peripapillary and macular regions are considered robust, current approaches commonly produce ILM segmentation errors at the ONH due to the presence of blood vessels and/or characteristic glaucomatous deep cupping. Because a precise segmentation of the ILM surface at the ONH is required for computing several newer structural measurements including Bruch's membrane opening-minimum rim width (BMO-MRW) and cup volume, in this study, we propose a multimodal multiresolution graph-based method to precisely segment the ILM surface within ONH-centered spectral-domain optical coherence tomography (SD-OCT) volumes. In particular, the gradient vector flow (GVF) field, which is computed from a multiresolution initial segmentation, is employed for calculating a set of non-overlapping GVF-based columns perpendicular to the initial segmentation. The GVF columns are utilized to resample the volume and also serve as the columns to the graph construction. The ILM surface in the resampled volume is fairly smooth and does not contain the steep slopes. This prior shape knowledge along with the blood vessel information, obtained from registered fundus photographs, are incorporated in a graph-theoretic approach in order to identify the location of the ILM surface. The proposed method is tested on the SD-OCT volumes of 44 subjects with various stages of glaucoma and significantly smaller segmentation errors were obtained than that of current approaches.

OCULAR HYPERTENSION AFTER INTRAVITREAL DEXAMETHASONE (OZURDEX) SUSTAINED-RELEASE IMPLANT.

PURPOSE: To evaluate ocular hypertension (OHT) after Ozurdex injection to determine the incidence of OHT, therapy for OHT, and any associative factors such as diagnosis, underlying glaucoma and therapy, or sequential Ozurdex injection(s). METHODS: Retrospective consecutive case series with patients receiving one or more intravitreal Ozurdex implantations at a tertiary care academic center. Ocular hypertension was defined as a single measurement of ≥30 mmHg or an increase of ≥10 mmHg from baseline. RESULTS: Ninety-four injections in 52 patients (59 eyes) were reviewed. Forty eyes received a single injection, and 19 eyes received multiple injections. Ocular hypertension developed in 14 patients (26.9%). Thirteen patients (25%) had preexisting glaucoma or suspicion of glaucoma, and 6 of these developed OHT. Glaucoma eye drops were initiated after 13 injections (13.8%). Invasive surgery for glaucoma was required in 3 patients (3.2%): all had glaucoma or suspicion of glaucoma (one case was related to neovascular glaucoma and unlikely related to steroid response after Ozurdex). There was no difference in relative intraocular pressure increase (i.e., difference between final follow-up or subsequent intravitreal injection vs. baseline) between single versus multiple Ozurdex injections (P = 0.883). CONCLUSION: Patients (26.9%) who received Ozurdex developed OHT. Glaucoma or glaucoma-suspicion factors were present in all patients who required invasive surgery for glaucoma. A greater proportion of patients who received multiple injections had an intraocular pressure elevation, but the relative intraocular pressure increase was not significant.

Multimodal registration of SD-OCT volumes and fundus photographs using histograms of oriented gradients.

With availability of different retinal imaging modalities such as fundus photography and spectral domain optical coherence tomography (SD-OCT), having a robust and accurate registration scheme to enable utilization of this complementary information is beneficial. The few existing fundus-OCT registration approaches contain a vessel segmentation step, as the retinal blood vessels are the most dominant structures that are in common between the pair of images. However, errors in the vessel segmentation from either modality may cause corresponding errors in the registration. In this paper, we propose a feature-based registration method for registering fundus photographs and SD-OCT projection images that benefits from vasculature structural information without requiring blood vessel segmentation. In particular, after a preprocessing step, a set of control points (CPs) are identified by looking for the corners in the images. Next, each CP is represented by a feature vector which encodes the local structural information via computing the histograms of oriented gradients (HOG) from the neighborhood of each CP. The best matching CPs are identified by calculating the distance of their corresponding feature vectors. After removing the incorrect matches the best affine transform that registers fundus photographs to SD-OCT projection images is computed using the random sample consensus (RANSAC) method. The proposed method was tested on 44 pairs of fundus and SD-OCT projection images of glaucoma patients and the result showed that the proposed method successfully registers the multimodal images and produced a registration error of 25.34 ± 12.34 µm (0.84 ± 0.41 pixels).

Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis).

PURPOSE: To investigate the role of TANK-binding kinase 1 (TBK1) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas. METHODS: In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas-juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)-using a quantitative polymerase chain reaction assay. RESULTS: No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucoma patients. CONCLUSIONS: TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucoma patient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma.

Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection.

PURPOSE: Medical treatment of glaucoma relies on intraocular pressure (IOP)-lowering medications, typically administered daily by the patient. While these medications are effective when applied correctly, patient adherence is a major obstacle in glaucoma treatment. We have developed a sustained-release formulation of timolol maleate that can be injected subconjunctivally to avoid patient noncompliance. METHODS: A biodegradable microsphere formulation for timolol maleate was injected subconjunctivally in normal rabbits. We measured timolol levels in tears, aqueous humor, vitreous humor, and serum of study rabbits. Furthermore, IOP profiles were recorded longitudinally. Tissue compatibility and side effects were evaluated using histochemistry. RESULTS: The microsphere formulation led to measureable amounts of timolol in the aqueous humor and the tear film for up to 90 days. Timolol was not detectable in the serum at any time. A significant reduction of IOP was observed in treated eyes. Clinically, the subconjunctival administration of the microspheres was well tolerated with no signs of inflammation or infection. The absence of local inflammation was confirmed by histology. CONCLUSIONS: A single subconjunctival administration of timolol microspheres achieved delivery and IOP reduction in rabbits for up to 90 days without local or systemic inflammation or toxicity. This approach has the potential to improve the management of glaucoma in patient populations, who are challenged to adhere to a regimen of daily eye drops.

Management of Pediatric Aphakic Glaucoma With Vitrectomy and Tube Shunts.

PURPOSE: To review the impact of vitrectomy and tube shunts on mean intraocular pressure (IOP) and number of glaucoma medications in pediatric aphakic glaucoma. METHODS: A retrospective review of pediatric patients who underwent combined vitrectomy and glaucoma tube shunt surgery for aphakic glaucoma was conducted. Inclusion criteria were: age 18 years or younger, diagnosis of aphakic glaucoma, preoperative IOP data, and postoperative IOP data for at least 6 months. Mean IOP lowering at 1 year, number of glaucoma medications at 1 year, and surgical complications, including tube occlusion in the postoperative period, were noted. RESULTS: The mean ± standard deviation preoperative IOP was 33.9 ± 10.6 mm Hg (range: 18 to 57 mm Hg) with a mean of three topical IOP-lowering medications. A total of 5 (36%) Ahmed and 9 (64%) Baerveldt tube shunts were placed. One of the Baerveldt tube shunt procedures was combined with revision of a traumatically dislocated tube. The mean IOP at 12 months postoperatively was 16.6 ± 5.8 mm Hg (range: 6 to 28 mm Hg; P < .01, t = 3.74, df = 13) with a mean of 2.3 glaucoma medications. There were no cases of tube occlusion, corneal decompensation, endophthalmitis, or retinal detachment over the 12 months of follow-up. CONCLUSIONS: Combined vitrectomy and placement of a glaucoma tube shunt can be safe and effective in lowering IOP based on mean IOP values and number of glaucoma medications at 1 year. [J Pediatr Ophthalmol Strabismus. 2016;53(6):339-343.].

SQSTM1 Mutations and Glaucoma.

Glaucoma is the most common cause of irreversible blindness worldwide. One subset of glaucoma, normal tension glaucoma (NTG) occurs in the absence of high intraocular pressure. Mutations in two genes, optineurin (OPTN) and TANK binding kinase 1 (TBK1), cause familial NTG and have known roles in the catabolic cellular process autophagy. TKB1 encodes a kinase that phosphorylates OPTN, an autophagy receptor, which ultimately activates autophagy. The sequestosome (SQSTM1) gene also encodes an autophagy receptor and also is a target of TBK1 phosphorylation. Consequently, we hypothesized that mutations in SQSTM1 may also cause NTG. We tested this hypothesis by searching for glaucoma-causing mutations in a cohort of NTG patients (n = 308) and matched controls (n = 157) using Sanger sequencing. An additional 1098 population control samples were also analyzed using whole exome sequencing. A total of 17 non-synonymous mutations were detected which were not significantly skewed between cases and controls when analyzed separately, or as a group (p > 0.05). These data suggest that SQSTM1 mutations are not a common cause of NTG.

Boston Type 1 Keratoprosthesis: Visual Outcomes, Device Retention, and Complications.

PURPOSE: To determine the visual outcomes, device retention, and complications after Boston type 1 keratoprosthesis (KPro-1) device implantation. METHODS: Comprehensive review of every case of KPro-1 implantation at a tertiary eye care center. RESULTS: The initial KPro-1 procedure, performed in 75 eyes without a previous keratoprosthesis, was included in the analysis. During the first 6 postoperative months, improvement occurred in the mean preoperative best-corrected visual acuity of 20/1265 to a mean best-obtained postoperative visual acuity of 20/97 (P < 0.001). After a mean follow-up period of 41.4 months (range, 0.8-82.8 months), the final mean best-corrected visual acuity was 20/428. Improved vision was recorded in 43 eyes (57.3%), ambulatory vision (≥20/400) in 47 eyes (62.7%), intermediate functional vision (≥20/80) in 23 eyes (30.7%), and full functional vision (≥20/40) in 11 eyes (14.7%). The initial device was retained in 64 eyes (85.3%), with a Kaplan-Meier retention probability of 96% at 6 months and 82% at 5 years. One or more sight-threatening complications occurred in 51 eyes (68%). These included device extrusion in 11 eyes (14.7%), ulcerative keratitis in 12 eyes (16%), endophthalmitis in 7 eyes (9.3%), sterile vitritis in 3 eyes (4%), retroprosthetic membranes in 25 eyes (33.3%), maculopathy in 26 eyes (34.7%), retinal detachment in 9 eyes (12%), and progressive optic neuropathy in 7 eyes (9.3%). CONCLUSIONS: Boston KPro-1 implantation is associated with satisfactory visual outcomes and excellent device retention in a majority of cases. However, serious postoperative complications are common and may compromise the final visual result.