Descemet membrane endothelial keratoplasty in eyes with COL8A2-associated corneal dystrophy.

Purpose: The p.(Leu450Trp) COL8A2 mutation, associated with an early-onset corneal endothelial dystrophy, can result in bullous keratopathy within the first few decades of life. People with this condition frequently experience anterior corneal changes in keratometry as the disease worsens, which may potentially affect refractive error after endothelial keratoplasty. We describe outcomes of the first cases of Descemet Membrane Endothelial Keratoplasty (DMEK) for patients with known mutations in this gene. Observations: Four eyes from two patients with COL8A2-associated corneal dystrophy underwent DMEK for this condition at a tertiary academic center. Preoperative and postoperative Scheimpflug imaging and manifest refraction was conducted. Mean central corneal thickness decreased from 713 µm preoperatively to 529 µm at one month. Despite long-standing corneal haze, all eyes reached between 20/20 and 20/30 best corrected visual acuity, and minimum postoperative central corneal thickness reached 482, 479, 479 and 533 µm. Refractive changes frequently occurred during the first postoperative year, with 3.6 D, 3.3 D, 3 D, and 0.8 D shifts in spherical equivalent taking place within this time period in the four eyes. Conclusions and Importance: In two patients with the p.(Leu450Trp) mutation in COL8A2 who underwent DMEK, resolution of corneal edema resulted in centrally thin corneas and refractive shifts postoperatively. Despite chronic edema, excellent visual acuity was achieved in all eyes.

In vivo MRI evaluation of early postnatal development in normal and impaired rat eyes.

This study employed in vivo 7-T magnetic resonance imaging (MRI) to evaluate the postnatal ocular growth patterns under normal development or neonatal impairments in Sprague-Dawley rats. Using T2-weighted imaging on healthy rats from postnatal day (P) 1 (newborn) to P60 (adult), the volumes of the anterior chamber and posterior chamber (ACPC), lens, and vitreous humor increased logistically with ACPC expanding by 33-fold and the others by fivefold. Intravitreal potassium dichromate injection at P1, P7, and P14 led to T1-weighted signal enhancement in the developing retina by 188-289%. Upon unilateral hypoxic-ischemic encephalopathy at P7, monocular deprivation at P15, and monocular enucleation at P1, T2-weighted imaging of the adult rats showed decreased ocular volumes to different extents. In summary, in vivo high-field MRI allows for non-invasive evaluation of early postnatal development in the normal and impaired rat eyes. Chromium-enhanced MRI appeared effective in examining the developing retina before natural eyelid opening at P14 with relevance to lipid metabolism. The reduced ocular volumes upon neonatal visual impairments provided evidence to the emerging problems of why some impaired visual outcomes cannot be solely predicted by neurological assessments and suggested the need to look into both the eye and the brain under such conditions.

CLOSTRIDIUM PERFRINGENS PANOPHTHALMITIS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION.

PURPOSE: This report describes a fulminant infection with Clostridium perfringens after an intravitreal anti-vascular endothelial growth factor injection. METHODS: This is a retrospective case review. RESULTS: Our patient's rapid infection eventually led to enucleation, despite broad-spectrum antibiotic therapy. CONCLUSION: Reporting rare causes and common clinical findings of C. perfringens ocular infection may lead to earlier detection and intervention.

Characteristics and Outcomes of Open Globe Trauma in the Urban versus Rural Population: A Single Center Retrospective Review.

PURPOSE: To examine the characteristics and outcomes of open globe injuries sustained by the urban population compared to the rural population. METHODS: This is a retrospective chart review of 429 patients presenting to University of Pittsburgh Medical Center (UPMC) Presbyterian Hospital with traumatic open globes from July 2005 to July 2013. RESULTS: Rural patients had a longer time which elapsed from injury to presentation (P = 0.023, average 12.04 hours vs 7.53 hours). There was a higher incidence of patient transfer prior to arrival to UPMC Presbyterian Hospital (P = 0.018), patient follow-up elsewhere (P = 0.049), and patients sustaining intraocular foreign bodies (IOFBs) (P = 0.009). CONCLUSIONS: Health care access is a well-known problem in rural areas and using rural-urban commuting area (RUCA) codes can help identify a population for risk factors or potential disparities in care. Rural patients sustained a higher rate of IOFBs; this should heighten the clinicians' suspicion during the evaluation of an open globe in other rural populations.

Management of Descemet Membrane Detachment After Forceps Birth Injury.

PURPOSE: To describe the clinical signs of Descemet membrane (DM) detachment due to forceps-related birth injury and its subsequent management using optical coherence tomography. METHODS: Case report. RESULTS: A 3-day-old term infant presented with left eye corneal clouding and a definitive history of traumatic forceps-assisted delivery. Despite topical therapy, corneal clouding persisted, necessitating an examination under anesthesia using ultrasound and handheld optical coherence tomography. This revealed not only a tear in DM but also a large detachment. Injection of air alone failed to achieve apposition of DM to the posterior stroma. Apposition was achieved only after penetration of the overlying cornea with the needle of a 10-0 nylon suture and release of clear viscous fluid. The cornea cleared within the first week and continued in the months to follow. CONCLUSIONS: Prolonged corneal edema should alert the physician to probable DM detachment after forceps-related birth injury. Injecting air alone may not be sufficient to reattach the detached DM.

In Vivo Evaluation of the Visual Pathway in Streptozotocin-Induced Diabetes by Diffusion Tensor MRI and Contrast Enhanced MRI.

Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI) was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively.

Long-term effects of neonatal hypoxia-ischemia on structural and physiological integrity of the eye and visual pathway by multimodal MRI.

PURPOSE: Neonatal hypoxia-ischemia is a major cause of brain damage in infants and may frequently present visual impairments. Although advancements in perinatal care have increased survival, the pathogenesis of hypoxic-ischemic injury and the long-term consequences to the visual system remain unclear. We hypothesized that neonatal hypoxia-ischemia can lead to chronic, MRI-detectable structural and physiological alterations in both the eye and the brain's visual pathways. METHODS: Eight Sprague-Dawley rats underwent ligation of the left common carotid artery followed by hypoxia for 2 hours at postnatal day 7. One year later, T2-weighted MRI, gadolinium-enhanced MRI, chromium-enhanced MRI, manganese-enhanced MRI, and diffusion tensor MRI (DTI) of the visual system were evaluated and compared between opposite hemispheres using a 7-Tesla scanner. RESULTS: Within the eyeball, systemic gadolinium administration revealed aqueous-vitreous or blood-ocular barrier leakage only in the ipsilesional left eye despite comparable aqueous humor dynamics in the anterior chamber of both eyes. Binocular intravitreal chromium injection showed compromised retinal integrity in the ipsilesional eye. Despite total loss of the ipsilesional visual cortex, both retinocollicular and retinogeniculate pathways projected from the contralesional eye toward ipsilesional visual cortex possessed stronger anterograde manganese transport and less disrupted structural integrity in DTI compared with the opposite hemispheres. CONCLUSIONS: High-field, multimodal MRI demonstrated in vivo the long-term structural and physiological deficits in the eye and brain's visual pathways after unilateral neonatal hypoxic-ischemic injury. The remaining retinocollicular and retinogeniculate pathways appeared to be more vulnerable to anterograde degeneration from eye injury than retrograde, transsynaptic degeneration from visual cortex injury.

Iris nevus growth into melanoma: analysis of 1611 consecutive eyes: the ABCDEF guide.

PURPOSE: To determine clinical features predictive of growth of iris nevus into melanoma. DESIGN: Retrospective, comparative case series. PARTICIPANTS: A total of 1611 consecutive patients referred to an ocular oncology center with iris nevus. INTERVENTION: Observation and photographic documentation. MAIN OUTCOME MEASURES: Growth into melanoma. RESULTS: The mean age at referral for iris nevus was 51 years (median, 54; range, <1-94 years). At presentation, the mean tumor basal diameter was 3 mm (median, 3 mm; range, <1-12 mm) and mean tumor thickness was 0.8 mm (median, 0.5 mm; range, 0-5 mm). All patients were initially diagnosed with benign iris nevus. Growth of iris nevus to melanoma was confirmed in 2% of eyes (n = 27) over a mean follow-up of 68 months (median, 46 months; range, 3-465 months). By Kaplan-Meier estimates, iris nevus growth to melanoma occurred in <1%, 3%, 4%, 8%, and 11% at 1, 5, 10, 15, and 20 years, respectively. Factors predictive of iris nevus growth to melanoma by multivariable analysis included age ≤ 40 years at presentation (hazard ratio [HR], 3), episode of hyphema (HR, 9), 4:00 to 9:00 clock hour location of tumor (HR, 9), diffuse tumor (involving entire iris surface) (HR, 14), ectropion uveae (HR, 4), and feathery tumor margins (HR, 3). Additional important factors by univariable analysis included tumor seeding on the iris or in the anterior chamber angle, feeder vessels, and nodule formation. These factors can be remembered using the mnemonic ABCDEF, representing A = age young, B = blood, C = clock hour inferior, D = diffuse, E = ectropion, and F = feathery margin. CONCLUSIONS: In an analysis of 1611 cases of iris nevus referred for evaluation at an ocular oncology center, growth into melanoma occurred in 8% by 15 years. Risk factors for growth, identified by ABCDEF included Age young, Blood (hyphema), Clock hour inferior, Diffuse configuration, Ectropion uveae, and Feathery tumor margin.

Clinical survey of 3680 iris tumors based on patient age at presentation.

OBJECTIVE: To report the spectrum of iris lesions based on patient age at presentation. DESIGN: Retrospective, nonrandomized, single-center case series. PARTICIPANTS: We included 3680 iris tumors in 3451 patients. METHODS: Chart review. MAIN OUTCOME MEASURES: Diagnostic category based on age. RESULTS: The mean age at presentation was 48 years and there were 449 (12%) tumors in children (≤20 years), 788 (21%) in young adults (21-40 years), 1308 (36%) in mid adults (41-60 years), and 1135 (31%) in senior adults (>60 years). Of 3680 tumors, the diagnostic category was cystic (n = 768; 21%) or solid (n = 2912; 79%). The cystic tumors originated from iris pigment epithelium (IPE; n = 672; 18%) or iris stroma (n = 96; 3%). The solid tumors included melanocytic (n = 2510; 68%) and nonmelanocytic (n = 402; 11%). The melanocytic tumors comprised nevus (n = 1503; 60%), melanocytoma (n = 68; 3%), melanoma (n = 645; 26%), and melanocytosis (n = 64; 3%). Of 2510 melanocytic tumors, the first and second most common diagnoses by age (children, young adult, mid adult, senior adult) were nevus (53%, 57%, 63%, and 63%, respectively) and melanoma (17%, 27%, 26%, and 27%, respectively). The nonmelanocytic tumors included categories of choristomatous (n = 4; <1%), vascular (n = 57; 2%), fibrous (n = 2; <1%), neural (n = 3; <1%), myogenic (n = 2;, <1%), epithelial (n = 35; 1%), xanthomatous (n = 8; <1%), metastasis (n = 67; 2%), lymphoid (n = 12; <1%), leukemic (n = 2; <1%), secondary (n = 12; <1%), and nonneoplastic simulators (n = 198; 5%). The median age (in years) at diagnosis included cystic (39), melanocytic (52), choristomatous (0.7), vascular (56), fibrous (53), neural (8), myogenic (42), epithelial (63), xanthomatous (1.9), metastasis (60), lymphoid (57), leukemic (25.5), secondary (59), and nonneoplastic simulators (49). Overall, the 3 most common specific diagnoses (children, young adult, mid adult, senior adult) were nevus (25%, 36%, 47%, and 47%, respectively), IPE cyst (28%, 30%, 15%, and 14%, respectively), and melanoma (8%, 16%, 20%, and 19%, respectively). CONCLUSIONS: In an ocular oncology practice, the spectrum of iris tumors includes cystic (21%) and solid (79%) tumors. The solid tumors were melanocytic (68%) or nonmelanocytic (11%). At all ages, the most common specific diagnoses were nevus (42%), IPE cyst (19%), and melanoma (17%).

Ocular surface squamous neoplasia (squamous cell carcinoma) of the socket: management of extensive tumors with interferon.

PURPOSE: To describe the clinical features and management of extensive ocular surface squamous neoplasia (OSSN) (squamous cell carcinoma) of the socket. METHODS: Retrospective interventional case series. Interferon α 2b (IFNa2b) eye drops (1 million units/cc) 4 times daily and IFNa2b sublesional injection (5 million units/0.5cc to 8 million units/0.8 cc) were delivered for tumor control. Participants were 3 patients with ocular prosthesis who developed extensive socket OSSN. Tumor control was graded as complete regression, partial regression, or no regression. RESULTS: OSSN was detected in the socket at age 60, 43, and 20 years in patients who had worn ophthalmic prostheses for 54, 26, and 13 years, respectively. The patients had chronic discharge and irritation (n = 3) managed with intermittent topical corticosteroids (n = 2). There were no predisposing factors of cigarette exposure, radiation exposure, eczema, systemic immune suppression, or organ transplantation. The prosthesis fit well with nonirritative edges. At presentation, OSSN was subtle (n = 3), vascular (n = 3), and multifocal (n = 3), with largest lesions or confluence of lesions measuring 20, 25, and 20 mm, respectively. The tumors involved the tarsal (n = 3), bulbar (n = 2), and forniceal (n = 2) surfaces. All patients were treated with topical and injection IFNa2b, with complete regression achieved in 2 cases (at 1 months and 20 months) and partial regression in one case (at 9 months). All patients continue on chronic maintenance IFNa2b topically. There were no recurrences, and IFNa2b injection side effects of nausea and chills were minor, lasting 1 day. No patient required surgical removal of tumors from the socket and no patient required exenteration. CONCLUSIONS: Patients wearing ophthalmic prosthesis over a socket should be monitored for the development of OSSN. Combined topical and injection IFNa2b could represent a potentially effective therapy for this condition.