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.

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.

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.

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.

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.

Orbital vicarious menstruation.

A 31-year-old African-American woman with a medical history of well-controlled hypertension sought treatment for recurrent, monthly, unilateral orbital and subconjunctival hemorrhage for 1 year. The episodes were cyclical and coincided with the timing of her menstrual cycle. Examination findings included right periorbital fullness and subconjunctival hemorrhage. Extensive serologic and radiographic workup ruled out other potential causes of recurrent orbital hemorrhage. The patient was diagnosed with orbital vicarious menstruation and treated with oral contraceptive pills, with marked clinical improvement.

Massive intracorneal cyst in a patient with no ocular symptoms.

OBJECTIVE: To report a rare case of intracorneal cyst with no ocular symptoms. METHODS: A case report of an intracorneal cyst that was treated with lubrication and intraocular pressure lowering medication is discussed. RESULTS: There was no increase in cyst size nor were there any new symptoms reported after 5 months of follow-up. CONCLUSIONS: Intracorneal cysts are believed to be caused by a sequestration of corneal limbal cells in the stroma from congenital or traumatic reasons. Because of the slow growing nature of intracorneal cysts, we highlight that surgical excision is not always warranted in patients, especially if the vision is already poor and if no symptoms are present.

Case report: spontaneous Stenotrophomonas maltophilia keratitis in a diabetic patient.

OBJECTIVES: To report a rare case of spontaneous Stenotrophomonas maltophilia keratitis in a diabetic patient. METHODS: A case report of this rare ulcerative keratitis case with an extensive review of the literature. RESULTS: The patient's corneal infiltrate was successfully cultured and a rare ocular organism identified. The patient's presentation and course and the response to empiric treatment are discussed. CONCLUSIONS: Consideration of the antibiotic combination chosen here can be considered in the treatment of S. maltophilia keratitis after appropriate cultures are taken and the organism isolated.

Repair of necrotizing scleritis in ulcerative colitis with processed pericardium and a Prokera amniotic membrane graft.

OBJECTIVES: To demonstrate an unusual case of necrotizing scleritis in ulcerative colitis successfully managed by a combination of a Prokera implant and processed pericardium. METHODS: A case report of a novel approach to treat scleral melts that may be seen in several clinical situations. RESULTS: The dual use of amniotic membrane material (Prokera) with processed tuttoplast for necrotizing scleritis salvaged the eye without the need for enucleation while also preserving most of the vision. CONCLUSIONS: Consideration of the combined method discussed in this article should be considered in the treatment of severe scleromalacia seen in inflammatory cases of the eye.

Repair of limbal dermoid with excision and placement of a circumlimbal pericardial graft.

OBJECTIVES: To report the treatment of a limbal dermoid tumor with excision of the lesion combined with the placement of a processed pericardial graft. METHODS: A case report of a new approach to treat large limbal dermoids after excision of the lesion from the cornea and limbus. RESULTS: The surgical result was very reasonable from a cosmetic result, and the patient recovered quite well. CONCLUSIONS: The use of processed pericardium on the scleral side of the lesion has not been reported previously with limbal dermoid excision. Intraoperatively, the abnormal tissue blended with the sclera and excision of perilimbal tissue was necessary to obtain a clear margin. One might want to consider the method described here for the treatment of large limbal dermoid lesions when the pathology seems indistinct at the conjunctival-corneal border during surgery.

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.

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.

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.

In vitro cytotoxic effects of benzalkonium chloride on adenovirus.

OBJECTIVE: To investigate the in vitro effects of benzalkonium chloride (BAK) at various concentrations and dosing schedules on adenoviral infection. METHODS: Adenovirus was placed in Refeed media and at 30 min after infection, various concentrations and doses of BAK were placed into the 1 mL solution. All assays were incubated at 37 degrees C. Dosing of BAK was performed for 3 days and qualitative viral immunofluorescence was compared with that of controls. RESULTS: BAK at multiple concentrations lysed the epithelial cell lines to varying degrees as did viral infection. Further, adenoviral infection was halted with many concentrations as well. CONCLUSIONS: Adenoviral infection was inhibited in vitro by different concentrations of BAK. CLINICAL RELEVANCE: Zymar solution which contains BAK could potentially have a role in the treatment of adenoviral ocular infection in humans.

Idiopathic superior keratectasia with spontaneous perforation treated with amniotic membrane transplantation.

PURPOSE: To demonstrate an unusual case of bilateral superior keratectasia complicated by a corneal perforation. METHODS: Case report of idiopathic superior keratectasia with a spontaneous perforation managed by amniotic membrane transplantation. RESULTS: Superior keratectasia was confirmed by a pattern of superior corneal steepening seen on corneal topography and keratometry in the fellow eye. CONCLUSIONS: Although rare, keratectasia with hydrops and a corneal perforation may present superiorly, and an amniotic membrane should be considered for management.

Circadian rhythm dysfunction in glaucoma: A hypothesis.

The absence of circadian zeitgebers in the social environment causes circadian misalignment, which is often associated with sleep disturbances. Circadian misalignment, defined as a mismatch between the sleep-wake cycle and the timing of the circadian system, can occur either because of inadequate exposure to the light-dark cycle, the most important synchronizer of the circadian system, or reduction in light transmission resulting from ophthalmic diseases (e.g., senile miosis, cataract, diabetic retinopathy, macular degeneration, retinitis pigmentosa, and glaucoma). We propose that glaucoma may be the primary ocular disease that directly compromises photic input to the circadian time-keeping system because of inherent ganglion cell death. Glaucomatous damage to the ganglion cell layer might be particularly harmful to melanopsin. According to histologic and circadian data, a subset of intrinsically photoresponsive retinal ganglion cells, expressing melanopsin and cryptochromes, entrain the endogenous circadian system via transduction of photic input to the thalamus, projecting either to the suprachiasmatic nucleus or the lateral geniculate nucleus. Glaucoma provides a unique opportunity to explore whether in fact light transmission to the circadian system is compromised as a result of ganglion cell loss.

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.

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.

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.

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.