Faculty Bibliography

PURPOSE: The study was performed to study the effect of cycloplegia on anterior chamber depth (ACD) in cataract eyes. One instrument (Lenstar) was used for all measurements. METHODS: Anterior chamber depth calculations were taken with the Lenstar in cataract eyes with a mean age of 71.9+/-8.8 years before instilling cycloplegic drops. Two drops of Tropicamide were then instilled in each eye and measurements were retaken between 30 to 45 min later. RESULTS: Cycloplegia with a mild agent used routinely in this practice location showed a statically significant effect on increasing ACD by 0.0647+/-0.01 in the OD and 0.0758+/-0.02 in the OS. CONCLUSIONS: Anterior chamber depth can be important in the final refractive result postcataract surgery. The results of a change in effective lens position would be most significant in higher intraocular lens powers.

We report a case of Descemet's membrane detachment after inadvertent intrastromal injection of hyaluronic acid. Surgical removal was attempted with minimal but slow improvement. Near-complete resolution occurred with subsequent conservative management within 6 weeks.

Most of the major morbidities in the preterm newborn are caused by or are associated with oxygen-induced injuries and are aptly called "oxygen radical diseases in neonatology or ORDIN". These include bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, intraventricular hemorrhage, necrotizing enterocolitis and others. Relative hyperoxia immediately after birth, immature antioxidant systems, biomolecular events favoring oxidative stress such as iron availability and the role of hydrogen peroxide as a key molecular mediator of these events are reviewed. Potential therapeutic strategies such as caffeine, antioxidants, non-steroidal anti-inflammatory drugs, and others targeted to these critical sites may help prevent oxidative radical diseases in the newborn resulting in improved neonatal outcomes.

Intravitreal bevacizumab (Avastin) use in preterm infants with retinopathy of prematurity is associated with severe neurological disabilities, suggesting vascular leakage. We examined the hypothesis that intermittent hypoxia (IH) potentiates intravitreal Avastin leakage. Neonatal rats at birth were exposed to IH from birth (P0)-P14. At P14, the time of eye opening in rats, a single dose of Avastin (0.125 mg) was injected intravitreally into the left eye. Animals were placed in room air (RA) until P23 or P45 for recovery (IHR). Hyperoxia-exposed and RA littermates served as oxygen controls, and equivalent volume saline served as the placebo controls. At P23 and P45 ocular angiogenesis, retinal pathology and ocular and systemic biomarkers of angiogenesis were examined. Retinal flatmounts showed poor peripheral vascularization in Avastin-treated and fellow eyes at P23, with numerous punctate hemorrhages and dilated, tortuous vessels with anastomoses at P45 in the rats exposed to IH. These adverse effects were associated with robust increases in systemic VEGF and in both treated and untreated fellow eyes. Histological analysis showed severe damage in the inner plexiform and inner nuclear layers. Exposure of IH/IHR-induced injured retinal microvasculature to anti-VEGF substances can result in vascular leakage and adverse effects in the developing neonate.

CYR61-CTGF-NOV (CCN)1 is a dynamically expressed extracellular matrix (ECM) protein with critical functions in cardiovascular development and tissue repair. Angiogenic endothelial cells (ECs) are a major cellular source of CCN1 which, once secreted, associates with the ECM and the cell surface and tightly controls the bidirectional flow of information between cells and the surrounding matrix. Endothelium-specific CCN1 deletion in mice using a cre/lox strategy induces EC hyperplasia and causes blood vessels to coalesce into large flat hyperplastic sinuses with no distinctive hierarchical organization. This is consistent with the role of CCN1 as a negative feedback regulator of vascular endothelial growth factor (VEGF) receptor activation. In the mouse model of oxygen-induced retinopathy (OIR), pericytes become the predominant CCN1 producing cells. Pericyte-specific deletion of CCN1 significantly decreases pathological retinal neovascularization following OIR. CCN1 induces the expression of the non-canonical Wnt5a in pericyte but not in EC cultures. In turn, exogenous Wnt5a inhibits CCN1 gene expression, induces EC proliferation and increases hypersprouting. Concordantly, treatment of mice with TNP470, a non-canonical Wnt5a inhibitor, reestablishes endothelial expression of CCN1 and significantly decreases pathological neovascular growth in OIR. Our data highlight the significance of CCN1-EC and CCN1-pericyte communication signals in driving physiological and pathological angiogenesis.

BACKGROUND: Caffeine or ketorolac decrease the risk of retinopathy of prematurity and may act synergistically to improve beneficial effect. Combination of caffeine (Caff) and ketorolac (Keto) to prevent oxygen-induced retinopathy was studied. METHODS: Newborn rats exposed to room air (RA) or intermittent hypoxia (IH) consisting of 12% O2 during hyperoxia (50% O2) from birth (P0) had single daily IP injections of Caff from P0-P13 or saline; and/or ocular Keto (Acuvail, 0.45% ophthalmic solution) administered subcutaneously over the eyes from P5-P7. Pups were studied at P14 or placed in RA for recovery from IH (IHR) until P21. Eyes were examined for neovascularization, histopathology, growth factors, and VEGF-signaling genes. RESULTS: Severe retinal damage noted during IHR in the untreated groups evidenced by hemorrhage, neovascularization, and oxygen-induced retinopathy (OIR) pathologies were prevented with Keto/Caff treatment. Keto and/or Caff treatment in IH also promoted retinal neural development evidenced by eye opening (92%, P < 0.001 vs. 31% in the placebo-treated IH group). No corneal pathologies were noted with Keto. CONCLUSION: Caff or Keto given individually reduced retinal neovascularization, but the two drugs given together prevented severe OIR.

Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are the keys in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, antioxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms, and synergistic approaches should be considered to maximize efficacy and safety.

INTRODUCTION: Infectious keratitis is a common ophthalmic disease with the potential for severe ocular morbidity. Multiple studies have described various risk factors for the development of infectious keratitis. The purpose of this study was to analyze the seasonal variation in the presentation of infectious keratitis, and also seasonal changes in its etiologies and risk factors. METHODS: A retrospective chart review was performed on consecutive patients presenting to the emergency department at our tertiary care urban hospital center who were diagnosed with infectious keratitis from 2008 to 2013. A chi-square analysis was performed to determine whether a significant seasonal variation existed between the month, season, frequency of presentation of ulcers, and other risk factors. RESULTS: A total of 155 patients-53 men and 102 women-with a mean age of 40 (range, 3-97; median, 36) diagnosed with infectious keratitis were included in the analysis. Sixty-nine (44.5%) ulcers presented in the summer, 19 (12.3%) in the fall, 34 (21.9%) in the winter, and 33 (21.3%) in the spring (P<0.0001). Seventeen (11%) patients experienced diabetes mellitus, 60 (39%) were contact lens wearers, 12 (8%) ulcers occurred in the setting of trauma, and 19 (12%) patients underwent previous ocular surgery. A total of 92 ulcers were cultured, of which 53.8% were positive in the summer, 42.9% in the fall, 55.0% in the winter, and 42.1% in the spring. A significant seasonal variation in the frequency of 1 organism, Pseudomonas aeruginosa, was identified (P=<0.0001); up to 47.6% of culture-positive ulcers in the summer were P. aeruginosa positive, whereas cultures in the remaining seasons were 0, 9.1% and 12.5% positive for this organism. DISCUSSION: The summer months have a higher frequency of infectious keratitis and P. aeruginosa positivity in this study. Possible factors leading to this increased summer presentation include warmer temperatures, higher humidity, and greater ocular exposure to water. Clinicians should increase their vigilance and education to high-risk patients during these periods and potentially modify empiric treatment regimens.

PURPOSE: Frequent, brief intermittent episodes of hypoxia (IH) during hyperoxia increase reactive oxygen species in the immature retina with compromised antioxidant systems, thus leading to oxygen-induced retinopathy (OIR). We examined the hypothesis that early exposure to a mimetic of superoxide dismutase (SOD), the first line of defense against oxidative stress, will decrease IH-induced reactive oxygen species (ROS) and prevent severe OIR in our rat model. METHODS: To test this hypothesis, newborn rats (P0) were exposed to IH consisting of alternating cycles of 50% O(2) with brief hypoxia (12% O(2)) until P14 during which they were treated with a single daily intraperitoneal (IP) dose of MnTBAP (a SOD mimetic) at 1.0, 5.0, or 10.0 mg/kg on P0, P1, and P2. A saline-treated group served as vehicle controls. Groups were analyzed following IH at P14 or allowed to recover in room air (RA) until P21. Control littermates were raised in RA with all conditions identical except for inspired O(2). Ocular assessment of OIR severity, oxidative stress, angiogenesis, antioxidant activity, and oxidative phosphorylation (OXPHOS) were conducted at P14 and P21. RESULTS: Collectively, the data show increased oxidative stress and angiogenesis with MnTBAP, which was associated with photoreceptor damage, retinal characteristics consistent with severe OIR, and changes in genes regulating OXPHOS. CONCLUSIONS: In the setting of IH, the use of exogenous SOD mimetics must be combined with H(2)O(2) scavengers in order to prevent photoreceptor damage and severe OIR.