MALT Lymphoma Presenting with Peripheral Ulcerative Keratitis.

Objective: To report a case of ocular mucosa-associated lymphoid tissue (MALT) lymphoma presenting with peripheral ulcerative keratitis. Methods: A 58-year-old man with a history of vitreous syneresis in both eyes and glaucoma presented with an abnormal, painful sensation of the left eye and mild hyperemia. Physical examination revealed peripheral ulcerative keratitis superiorly and a salmon-colored lesion in the superior conjunctiva. Results: The differential diagnosis of superior corneal thinning includes collagen vascular disease, Terrien's marginal degeneration, infectious keratitis, and other forms of peripheral keratitis. Our patient was diagnosed with conjunctival MALT lymphoma by surgical excision of the mass, and the peripheral ulcerative keratitis may be related to this diagnosis. Conclusion: Although rare, this case demonstrates a peripheral keratitis possibly related to the underlying disease of MALT lymphoma. The patient is being treated with local radiation treatment.

POSITION OF IN-THE-BAG POSTERIOR CHAMBER INTRAOCULAR LENSES RELATIVE TO THE LIMBUS: Applications to Scleral-Sutured Lenses.

PURPOSE: To characterize the true position of in-the-bag intraocular lenses (IOLs) relative to the limbus using ultrasound biomicroscopy and estimate scleral-sutured IOL positioning. METHODS: This prospective single-center study included 70 eyes of 41 patients with in-the-bag posterior chamber IOLs. Four vertical ultrasound biomicroscopy captures were performed in each eye in the superior, inferior, nasal, and temporal quadrants. Postoperative biometric data were collected. The primary outcome was the vertical distance of the in-the-bag IOL from the sclerocorneal limbus. Secondary outcomes included anterior shift and refractive change of a theoretical scleral-sutured IOL using sclerotomies at 2.5 mm and 3 mm posterior to the limbus. RESULTS: A total of 265 ultrasound biomicroscopy images were analyzed, including 64 superior, 69 inferior, 66 nasal, and 66 temporal. The true in-the-bag IOL position measured as distance posterior to the sclerocorneal limbus was 4.23 ± 0.56 mm superiorly, 4.22 ± 0.46 mm inferiorly, 3.95 ± 0.48 mm nasally, and 3.86 ± 0.52 mm temporally. The anterior shift of a theoretical scleral-sutured IOL was 0.60 mm for a 3-mm sclerotomy and 0.93 mm for a 2.5-mm sclerotomy, resulting in a theoretical myopic shift of 0.45 diopter (D) and 0.79 D, respectively, assuming a 15-D IOL. Larger biometric measurements correlated with a more posterior in-the-bag position. CONCLUSION: True in-the-bag IOL position was found to be more posterior than estimates of scleral-sutured IOLs. Additional corrections in scleral-sutured IOL calculations may improve refractive outcomes.

Pseudopemphigoid: Sarcoidosis presenting as cicatricial conjunctivitis with symblepharon.

Conjunctival involvement in sarcoidosis is commonly characterized by epibulbar nodules or follicular conjunctivitis. The authors describe an apparently healthy woman who developed extensive monocular cicatricial conjunctivitis with symblepharon. The array of conditions presenting with cicatricial conjunctivitis was considered, with mucous membrane pemphigoid leading the diagnostic possibilities. Conjunctival biopsy disclosed the non-infectious, non-caseating granulomas of sarcoidosis and a systemic evaluation disclosed pulmonary nodules and hilar lymphadenopathy. As the patient had no respiratory symptoms and an old history of hepatic steatosis, oral hydroxychloroquine and topical cyclosporin were chosen for therapy rather than systemic corticosteroids.

An adult with COVID-19 kawasaki-like syndrome and ocular manifestations.

PURPOSE: The severe acute respiratory syndrome coronavirus-2 and its associated infection known as COVID-19 have resulted in a global pandemic. Ocular manifestations of COVID-19 are nonspecific and include hyperemia, chemosis, epiphora, secretions, and eyelid edema. There is a paucity in the literature regarding COVID-19 related inflammatory syndromes which may also include ocular manifestations. OBSERVATIONS: In pediatric patients, conjunctivitis has been recently reported in association with a multisystem inflammatory condition related to COVID-19 that shares features with Kawasaki disease and toxic shock syndrome. We describe the clinical course of an adult patient with symptoms and signs consistent with a Kawasaki-like syndrome. CONCLUSIONS AND IMPORTANCE: To our knowledge, this report may be the first case of a Kawasaki-like syndrome in an adult with COVID-19 infection.

Dupilumab-Associated Blepharoconjunctivitis with Giant Papillae.

PURPOSE: To describe a case of severe dupilumab-associated blepharoconjunctivitis with giant papillae treated with high potency corticosteroid eyedrops, without discontinuing or reducing dupilumab therapy. CASE REPORT: A 22-year-old Latin American female with a long history of severe atopic dermatitis (AD) with no ocular involvement presented 20 weeks after starting treatment with dupilumab injections with blurry vision, multiple chalazia, eyelid swelling and severe conjunctival injection in both eyes. She also reports having a hordeolum 2 months prior and severely dry eyes starting 2 weeks prior. Slit-lamp examination revealed severe conjunctivitis with macroscopically visible giant papillae in the right lower tarsal conjunctiva. The diagnosis of severe dupilumab-associated blepharoconjunctivitis was made and difluprednate 0.05% eyedrops two times a day for 7 days was initiated. Given the severity of her AD and her marked skin improvement with dupilumab, it was decided to continue dupilumab without reducing the dose. At 2-day follow-up, conjunctival injection had markedly improved, and at 2-month follow-up, her examination was unremarkable. Currently, our patient only uses dexamethasone 0.1% drops few times a week as per needed for occasional eye irritation. CONCLUSION: As dupilumab injections begin to claim a rightful place in medicine, the ophthalmic community may start encountering dupilumab-associated ocular surface disease all more often and potentially play an important role in identifying, characterizing and treating the adverse ocular effects from this novel medication.

A case of hypertrophic herpes simplex virus affecting the eyelid and cornea masquerading as IgG4-related disease.

PURPOSE: To report a case of hypertrophic herpes simplex virus (HSV) of the eyelid and cornea masquerading as IgG4-related disease. OBSERVATIONS: A 37-year old African American female with a past medical history of human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART) and a recent history of treated genital herpes, presented with an ulcerative lesion of the left upper and lower eyelids, and severe ocular inflammation with symblepharon. Initially, eyelid biopsy revealed findings consistent with IgG4-related disease, and the patient was treated with high dose oral prednisone. After one week of therapy, there was no improvement in the patient's symptoms, and she subsequently developed a corneal epithelial defect which progressed to chronic ulceration. Repeat biopsy and corneal cultures revealed herpes simplex virus type 2. The patient was treated with high dose acyclovir, and the lid lesion improved. The conjunctival inflammation and corneal epithelial defect resolved but symblepharon restricting her eye movement remained. She also developed corneal vascularization and opacification causing severe vision loss. CONCLUSIONS AND IMPORTANCE: Chronic hypertrophic herpes simplex virus infection is a rare condition reported in patients with HIV. While there have been few reports of hypertrophic HSV affecting the eyelid, this is the first reported case of hypertrophic HSV affecting the eye, resulting in severe vision loss.

Human retinal endothelial cells and astrocytes cultured on 3-D scaffolds for ocular drug discovery and development.

Topical ocular ketorolac improves the outcomes of severe retinopathy of prematurity and when administered with systemic caffeine, decreases the severity of oxygen-induced retinopathy. We tested the hypothesis that co-cultures of human retinal endothelial cells (HRECs) and human retinal astrocytes (HRAs) on 3-dimensional (3-D) hydrogel scaffolds is a more representative biomimetic paradigm of the blood-retinal-barrier (BRB) than 2-D cultures, and should be utilized for preclinical drug discovery and development. Mono- and co-cultures of HRECs and HRAs were treated with standard doses of ketorolac, ibuprofen, and/or caffeine, and exposed to hyperoxia, intermittent hypoxia (IH), or normoxia on 2-D surfaces or 3-D biodegradable hydrogel scaffolds (AlgiMatrix or Geltrex). Media and cells were collected at 72h post treatment for arachidonic acid metabolites. Cells cultured on 3-D scaffolds exhibited less oxidative stress and variability in drug responses. HRAs enhanced the responses of HRECs to drugs and changes in oxygen environment. PGE2 and PGI2 were the predominant prostanoids produced in response to IH, reflecting COX-2 immunoreactivity. We conclude that HRECs and HRAs co-cultured on 3-D scaffolds may recapitulate drug responses of the dynamic BRB and therefore should be implemented for preclinical ocular drug discovery and development.

Evaluation of the Effect of Cycloplegia on Anterior Chamber Depth in Cataract Patients Using Optical Low-Coherence Reflectometry.

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.

Gout Keratitis: A Case of Peripheral Ulcerative Keratitis Secondary to Gout With a Review of the Literature.

PURPOSE: To report a case of peripheral ulcerative keratitis secondary to gout. METHODS: A 41-year-old man with a history of severe gout disease presented with pain and redness of the right eye. Physical examination revealed 2 areas of peripheral corneal thinning with overlying epithelial defects. Adjacent to these areas, reflective crystals were identified in the corneal stroma. Anterior segment optical coherence tomography demonstrated stromal corneal deposits. RESULTS: Systemic workup was negative aside from an elevated serum uric acid level. The patient was administered oral prednisone, allopurinol, and colchicine. At his 2-month follow-up visit, the patient was asymptomatic and his corneal thinning had significantly improved. CONCLUSIONS: Gout is the most common type of inflammatory arthritis in adults with rising incidence and prevalence. Ocular findings in gout are common, but patients are usually asymptomatic. Monosodium urate crystal deposition has been reported to occur in various parts of the eye, with and without ocular inflammation. Crystal deposition in the cornea is extremely rare and may be a cause of peripheral ulcerative keratitis.

Descemet's Membrane Dehiscence Resulting From Misdirected Viscoelastic During Anterior Chamber Reformation.

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.

Ocular Adverse Effects of Intravitreal Bevacizumab Are Potentiated by Intermittent Hypoxia in a Rat Model of Oxygen-Induced Retinopathy.

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.

Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy.

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.

Neonatal Intermittent Hypoxia, Reactive Oxygen Species, and Oxygen-Induced Retinopathy.

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.

Pharmacologic synergism of ocular ketorolac and systemic caffeine citrate in rat oxygen-induced retinopathy.

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.

Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity.

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.

Seasonal Variation in the Presentation of Infectious Keratitis.

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.

Single and Compound Knock-outs of MicroRNA (miRNA)-155 and Its Angiogenic Gene Target CCN1 in Mice Alter Vascular and Neovascular Growth in the Retina via Resident Microglia.

The response of the retina to ischemic insult typically leads to aberrant retinal neovascularization, a major cause of blindness. The epigenetic regulation of angiogenic gene expression by miRNAs provides new prospects for their therapeutic utility in retinal neovascularization. Here, we focus on miR-155, a microRNA functionally important in inflammation, which is of paramount importance in the pathogenesis of retinal neovascularization. Whereas constitutive miR-155-deficiency in mice results in mild vascular defects, forced expression of miR-155 causes endothelial hyperplasia and increases microglia count and activation. The mouse model of oxygen-induced retinopathy, which recapitulates ischemia-induced aberrant neovessel growth, is characterized by increased expression of miR-155 and localized areas of microglia activation. Interestingly, miR-155 deficiency in mice reduces microglial activation, curtails abnormal vessel growth, and allows for rapid normalization of the retinal vasculature following ischemic insult. miR-155 binds to the 3'-UTR and represses the expression of the CCN1 gene, which encodes an extracellular matrix-associated integrin-binding protein that both promotes physiological angiogenesis and harnesses growth factor-induced abnormal angiogenic responses. Single CCN1 deficiency or double CCN1 and miR-155 knock-out in mice causes retinal vascular malformations typical of faulty maturation, mimicking the vascular alterations of miR-155 gain of function. During development, the miR-155/CCN1 regulatory axis balances the proangiogenic and proinflammatory activities of microglia to allow for their function as guideposts for sprout fusion and anastomosis. Under ischemic conditions, dysregulated miR-155 and CCN1 expression increases the inflammatory load and microglial activation, prompting aberrant angiogenic responses. Thus, miR-155 functions in tandem with CCN1 to modulate inflammation-induced vascular homeostasis and repair.

Clinical Course of Unilateral Acanthamoeba Keratitis in a Cosmetic Contact Lens Wearer.

PURPOSE: To report the features and clinical course of Acanthamoeba keratitis in a cosmetic contact lens wearer. CASE REPORT: A 29-year-old man sought medical attention for severe ocular pain, blurry vision, photophobia, and a foreign body sensation in the left eye for the past 3-4 days. He had been wearing a single sapphire cosmetic soft contact lens for 1-2 months. The left upper eyelid was edematous and the conjunctiva was hyperemic; the best corrected distance visual acuity was 20/400. A slit lamp examination revealed circular and perineural linear stromal opacities and diffuse keratic precipitates. A clinical diagnosis of herpes simplex keratitis was made and the patient was started on antiviral therapy. After initial improvement, the patient returned with worsening pain and vision; the corneal lesions had exacerbated. Unresponsiveness to antiviral therapy prompted examination of corneal scrapings, which revealed Acanthamoeba developmental forms. Antimicrobial therapy was prescribed resulting in relief of symptoms despite corneal opacities and poor vision. CONCLUSION: This case illustrates the importance of considering Acanthamoeba keratitis in contact lens wearers at presentation, particularly in those with symptomatic keratitis unresponsive to antiviral and antifungal therapy.

Exogenous Superoxide Dismutase Mimetic Without Scavenging H2O2 Causes Photoreceptor Damage in a Rat Model for Oxygen-Induced Retinopathy.

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% O2 with brief hypoxia (12% O2) 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 O2. 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 H2O2 scavengers in order to prevent photoreceptor damage and severe OIR.