Acute Calcific Band Keratopathy as an Adverse Effect of Recombinant Human Nerve Growth Factor (Cenegermin): A Multicenter Case Series.

PURPOSE: Cenegermin, (OXERVATE) a recently Food and Drug Administration-approved topical formulation of recombinant human nerve growth factor, has been used for the treatment of neurotrophic keratopathy (NK). Corneal deposits have been previously reported as a potential adverse effect; however, the clinical characteristics, visual significance, and treatment options have not been fully described. The purpose of this article is to better characterize corneal deposits occurring during treatment with cenegermin for neurotrophic keratopathy. METHODS: This was a retrospective, multicenter consecutive case series. RESULTS: We identified 5 patients from 3 institutions who developed a white opacity in varying layers of the cornea, consistent with calcium deposition, during treatment with cenegermin. In all cases, the opacity occurred rapidly over the course of a few weeks after initiation of treatment. Histopathologic examination of the cornea from one corneal patient demonstrated extensive calcification of the stroma extending to 90% depth. Before treatment, all patients had stage 2 or 3 NK (Mackie classification). The deposits were visually significant in all patients and did not resolve after cessation of cenegermin. There were no differences in age, sex, etiology of the NK, corneal transplant status, or concurrent medications between the patients who developed a deposit and 15 other patients with stage 2 or 3 NK who did not. One patient was successfully treated with superficial keratectomy with ethylenediaminetetraacetic acid chelation, one patient underwent penetrating keratoplasty, and one patient received a Boston keratoprosthesis. CONCLUSIONS: We report the rapid onset of a corneal opacity after initiation of treatment with cenegermin in patients with stage 2 or 3 NK, consistent with acute calcific band keratopathy. This visually significant adverse finding has not previously been described. We could not identify any risk factors for development. We recommend close monitoring of patients receiving cenegermin therapy because the opacity may be irreversible and may require keratoplasty for visual rehabilitation.

Human Brain Mapping of Visual Script Familiarity between Phonological and Logographic Language: 3 T Functional MRI Study.

Neurolinguistic circuitry for two different scripts of language, such as phonological scripts (PhonoS) versus logographic scripts (LogoS) (e.g., English versus Chinese, resp.), recruits segregated neural pathways according to orthographic regularity (OrthoR). The purpose of this study was to identify the effect of VSF for cortical representation according to different OrthoR to represent Hangul versus Hanja as PhonoS versus LogoS, respectively. A total of 24 right-handed, native Korean undergraduate students with the first language of PhonoS and the second language of LogoS were divided into high- or low-competent groups for L2 of LogoS. The implicit word reading task was performed using Hanja and Hangul scripts during functional magnetic resonance imaging (fMRI) acquisition. Fluctuations of fMRI BOLD signal demonstrated that the LogoS was associated with the ventral pathway, whereas PhonoS was associated with the dorsal pathway. By interaction analysis, compared with high-competent group, low-competent group showed significantly greater activation for Hanja than for Hangul reading in the right superior parietal lobule area and the left supplementary motor area, which might be due to neural efficiency such as attention and cognition rather than core neurolinguistic neural demand like OrthoR processing.

The Boston Ocular Surface Prosthesis as a novel drug delivery system for bevacizumab.

Corneal neovascularization causes deterioration of visual acuity and increases surface irregularities. Various techniques have been employed to help control the progression of corneal neovascularization; bevacizumab is a medication that targets the specific pathway of corneal neovascularization. The Boston Ocular Surface Prosthesis (BOSP) is a large diameter contact lens that aids in maintaining corneal surface integrity and may serve as a delivery system for topical bevacizumab. This paper reviews five patients who were treated with topical bevacizumab in their BOSP. All patients demonstrated improvement in their visual acuity and clinical exam. No adverse reactions were noted.

Central corneal thickness measured by the Orbscan II system, contact ultrasound pachymetry, and the Artemis 2 system.

PURPOSE: To compare central corneal thickness (CCT) measurements by the Orbscan II device, contact ultrasound (US) pachymetry, and the noncontact Artemis 2 scanning US system. SETTING: Department of Ophthalmology, Weill Cornell Medical College, New York, New York, USA. METHODS: The CCT in 40 eyes (20 normal subjects) was measured by the Orbscan II followed by contact US pachymetry and then the Artemis 2. Results were compared using analysis of variance (ANOVA), paired t tests, and Bland-Altman plots. RESULTS: There was a significant difference in CCT measurements between the 3 modes (F = 32.84, P = .0001, 1-way ANOVA). Artemis 2 and US pachymetry measurements were highly correlated (r2 = 0.963, P < .0001), although Artemis 2 values were a mean of 11.2 microm +/- 6.6 (SD) thinner than pachymetry values. Artemis 2 and Orbscan II measurements were less well correlated (r2 = 0.851, P < .001); Orbscan II values were a mean of 7.5 +/- 15.7 microm thinner than Artemis 2 values. Orbscan II values showed a trend toward increasing underestimation of CCT in thinner corneas. CONCLUSIONS: Ultrasound pachymetry and Artemis 2 CCT measurements were highly correlated; the 11 microm mean difference in measurements may be attributed to decentration, oblique incidence of the probe to the cornea, or possibly the effect of topical anesthesia with contact pachymetry. Although the mean difference between Orbscan II and Artemis 2 values was 7.5 microm, Orbscan values were less correlated than Artemis 2 values with contact US pachymetry and were prone to underestimation of the CCT in thinner corneas.

Development of visual acuity in children with cerebral visual impairment.

OBJECTIVE: To study the development of visual acuity in term-born children with cerebral visual impairment and a history of neonatal hypoxic-ischemic encephalopathy. METHODS: We studied 19 term-born children, aged 6 months to 6 years, with moderate to severe neonatal hypoxic-ischemic encephalopathy and behaviors indicative of cerebral visual impairment. Longitudinal measures of grating acuity were obtained using preferential looking (PL) and visual evoked potential (VEP) procedures. Visual acuities at first and last visits were compared. The courses of acuity development in the 9 children who underwent both VEP and PL acuity assessment at 4 or more ages were compared with normal development. RESULTS: All children had measurable PL and VEP acuity, despite poor visual behavior. In nearly all, both PL and VEP acuity were below normal for age. For both PL and VEP measures, acuity at the last visit was, on average, 1 octave better than at the first visit, with a rate of improvement lower than normal. Although parallel courses of PL and VEP development occurred in many, substantial disparities in PL and VEP acuity were observed in others. CONCLUSIONS: Modest increases in PL and VEP grating acuity occur during early childhood in many of these patients. The rate of increase is lower than normal.

Recurrent scleral abscess after uncomplicated cataract extraction.

PURPOSE: To report the unusual occurrence of a recurrent scleral abscess after uncomplicated cataract extraction. METHODS: Case report of a 77-year-old healthy woman. RESULTS: Multiple cultures and antibiotic treatments failed to resolve presenting symptoms. Gram stain, Gomori methenamine silver (GMS) stain, and all cultures were negative. After drainage of the abscess, the patient's symptoms cleared briefly, then returned 6 months later showing a positive GMS stain consistent with Candida. The patient was treated with amphotericin, natamycin, and fluconazole at this time, and a return in visual acuity occurred along with a resolution of symptoms. No re-occurrence has been noted with 2.5 years of follow-up. CONCLUSIONS: Cataract extraction, although generally a safe procedure, can still result in unusual complications such as scleral abscesses. Excellent outcomes are possible once the infections are identified and treated.

Growth factor, cytokine and protease interactions during corneal wound healing.

Healing of corneal injuries is an exceptionally complex process involving the integrated actions of multiple growth factors, cytokines, and proteases produced by epithelial cells, stromal keratocytes, inflammatory cells, and lacrimal gland cells. Following corneal injury, basal epithelial cells migrate and proliferate in response to chemotactic cytokines and mitogenic growth factors, including epidermal growth factor and keratinocyte growth factor. Simultaneously, keratocytes adjacent to the injured area undergo apoptosis under the Fas/Fas ligand system, while more distant keratocytes transform into activated fibroblasts and migrate into the wound, where they begin synthesizing new extracellular matrix components that form the scar tissue under the dominant influence of the TGFb/ CTGF system. Epithelial cells and activated stromal fibroblasts also secrete growth factors and cytokines that have paracrine and autocrine functions. Corneal repair proceeds for the next several weeks to months, during which time the gene expression profile slowly returns to the pre-injury pattern and the provisional scar matrix slowly remodels by actions of matrix metalloproteinases. While minor epithelial injuries heal by regeneration of normal architecture, large stromal injuries heal by repair with irregular scar tissue that impairs the optical properties of the cornea.Also, if the integrated regulation of the wound healing process is interrupted at any point, the wound fails to heal properly and a corneal ulcer develops. Better understanding of the cellular and molecular changes that occur during repair of corneal wounds will provide the opportunity to design agents that selectively modulate key phases of corneal wound healing, resulting in scars that more closely resemble normal corneal architecture.