Extranodal Rosai-Dorfman Disease of the Orbit: Clinical Features of 8 Cases.

PURPOSE: To report on the presentation, radiography, histology, and treatment of 8 cases of extranodal Rosai-Dorfman disease involving the orbit. METHODS: Multicenter retrospective case series. RESULTS: Five males and 3 females had a median age of 10 years (range 2-78 years). Presenting signs and symptoms included proptosis, periorbital pain, palpable mass, blepharoptosis, decreased vision, diplopia, impaired extraocular motility, and afferent pupillary defect. Four patients had bilateral orbital disease, while 4 had unilateral disease. Six cases were extraconal, 1 was intraconal, and 1 was both intra- and extra-conal. Four cases had only extranodal disease without lymphadenopathy (3 of which had localized orbital disease). Diagnosis was confirmed by exam, orbital, and/or systemic radiography, and biopsy in all cases. Treatment strategies included excision or debulking, systemic corticosteroids, chemotherapy, radiotherapy, observation or a combination thereof. At last follow up, 4 patients were disease free, while 4 had residual improved disease. CONCLUSIONS: Rosai-Dorfman disease of the orbit is a rare clinical entity. Purely extranodal disease is rare, with isolated orbital disease being exceedingly rare. This study is unique in that 4 of 8 patients had strictly isolated extranodal disease of the orbit. A large majority of the cases had disease in the extraconal space, contrasting with previous reports. In addition, lacrimal gland disease, particularly bilateral involvement, was prominent in the current study. Although there is no consensus on treatment, surgical excision should be attempted if plausible in symptomatic patients especially if the orbit represents a localized site of disease.

The molecular genetics of eyelid tumors: recent advances and future directions.

BACKGROUND: Unprecedented recent advances in the molecular genetics of cutaneous malignancies have markedly improved our ability to diagnose, treat, and counsel patients with skin tumors. This review provides an update on molecular genetics of periocular cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous carcinoma, Merkel cell carcinoma, and malignant melanoma and describes how the knowledge of molecular genetics is translated into clinical practice. METHODS: A literature search of peer-reviewed and indexed publications from 1965 to 2012 using the PubMed search engine was performed. Key terms included: molecular genetics, eyelid, basal cell carcinoma, squamous cell carcinoma, sebaceous adenoma, sebaceous epithelioma, sebaceoma, sebaceous carcinoma, Merkel cell carcinoma, and melanoma. Seminal articles prior to 1965 were selected from primary sources and reviews from the initial search. Articles were chosen based on pertinence to clinical, genetic, and therapeutic topics reviewed in this manuscript. RESULTS: We reviewed the literature regarding the advances in molecular genetics of cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous neoplasia, Merkel cell carcinoma, and malignant melanoma, and possible future directions towards diagnosing and treating cutaneous tumors at the genetic level. Cell culture experiments, animal models, and molecular genetic studies on the patients' tumor tissues helped to elucidate genetic aberrations in these lesions. Cell culture experiments, animal studies and, ultimately, clinical trials provided means to test and develop novel therapeutic strategies, namely targeted therapy directed at specific molecular genetic defects. While remarkable progress has been made in this process, the complexity of the molecular genetics of skin tumors makes complete elucidation of the genetic mechanisms and the search for ideal therapies challenging. CONCLUSIONS: The recent studies focusing on molecular genetics of cutaneous malignancies show promising results, thereby improving our ability to diagnose, treat and counsel patients with these lesions. Future studies will hopefully help unravel further molecular mechanisms involved in cutaneous neoplasia and provide insights into novel preventative and therapeutic modalities.

Infected epithelial inclusion cyst simulating conjunctival melanoma.

There are several pigmented nonneoplastic lesions that can clinically simulate melanocytic tumors. The authors report an unusual conjunctival epithelial inclusion cyst that contained luminal bacterial colonies, hemorrhage, and epithelial debris. Clinical appearance convincingly simulated a melanoma. The clinical and histopathologic features of this lesion are discussed.

Effects of melatonin and its receptor antagonist on retinal pigment epithelial cells against hydrogen peroxide damage.

PURPOSE: Recently, we reported finding that circulating melatonin levels in age-related macular degeneration patients were significantly lower than those in age-matched controls. The purpose of this study was to investigate the hypothesis that melatonin deficiency may play a role in the oxidative damage of the retinal pigment epithelium (RPE) by testing the protective effect of melatonin and its receptor antagonist on RPE cells exposed to H(2)O(2) damage. METHODS: Cultured human RPE cells were subjected to oxidative stress induced by 0.5 mM H(2)O(2). Cell viability was measured using the microculture tetrazoline test (MTT) assay. Cells were pretreated with or without melatonin for 24 h. Luzindole (50 µM), a melatonin membrane-receptor antagonist, was added to the culture 1 h before melatonin to distinguish direct antioxidant effects from indirect receptor-dependent effects. All tests were performed in triplicate. RESULTS: H(2)O(2) at 0.5 mM decreased cell viability to 20% of control levels. Melatonin showed dose-dependent protective effects on RPE cells against H(2)O(2). Cell viability of RPE cells pretreated with 10(-10), 10(-8), 10(-6), and 10(-4) M melatonin for 24 h was 130%, 160%, 187%, and 230% of cells treated with H(2)O(2) alone (all p<0.05). Using cells cultured without H(2)O(2) as the control, cell viability of cells treated with H(2)O(2) after pretreatment with 10(-10)-10(-4) M melatonin was still significantly lower than that of the controls, suggesting that melatonin significantly decreased but did not completely abolish the in vitro cytotoxic effects of H(2)O(2). Luzindole completely blocked melatonin's protective effects at low concentrations of melatonin (10(-10)-10(-8) M) but not at high concentrations (10(-6)-10(-4) M). CONCLUSIONS: Melatonin has a partial protective effect on RPE cells against H(2)O(2) damage across a wide range of concentrations (10(-10)-10(-4) M). This protective effect occurs through the activation of melatonin membrane receptors at low concentrations (10(-10)-10(-8) M) and through both the direct antioxidant and indirect receptor activation effects at high concentrations (10(-6)-10(-4) M).

Plasmacytoma associated with canaliculitis.

Plasmacytomas are plasma cell neoplasms that rarely involve ocular adnexal tissues as a primary lesion or secondary manifestation of plasma cell myeloma. Only one case of plasmacytoma involving the lacrimal drainage system, to our knowledge, is described in the literature. The clinical presentation of ocular adnexal primary plasmacytoma typically relates to its mass effect. In this clinicopathologic report, we describe an unusual presentation of primary plasmacytoma of the lacrimal canaliculus as infectious canaliculitis.

Syringocystadenocarcinoma papilliferum of the eyelid.

An 86-year-old man presented with an ulcerated, painless right lower eyelid lesion of unknown duration. Excisional biopsy was performed to rule out suspected basal cell carcinoma. Pathologic evaluation demonstrated syringocystadenocarcinoma papilliferum. Three months after complete excision of the tumor, the patient remains well with no evidence of local recurrence or metastases. Review of the literature identified 20 cases of syringocystadenocarcinoma papilliferum, none of which presented in the skin of the ocular adnexa. The authors review the typical presentation, clinical course, and outcome of patients with syringocystadenocarcinoma papilliferum and compare these data to the case presented here.

Shifting trends in in vitro antibiotic susceptibilities for common bacterial conjunctival isolates in the last decade at the New York Eye and Ear Infirmary.

BACKGROUND: Bacterial conjunctivitis is one of the most common forms of ocular diseases worldwide. The purpose of this study is to determine the most common pathogens causing bacterial conjunctivitis, their in vitro susceptibility to existing antibiotics, and the changing trends in bacterial resistance to antibiotics over the last decade. METHODS: Records of all conjunctival bacterial cultures performed at the NYEEI Microbiology Laboratory from 1 January 1997 through 30 June 2008 were reviewed. Data on species of bacterial isolates and their in vitro susceptibility to the antibiotics tetracycline, trimethaprim/sulfamethoxazole (TMP/SMZ), imipenem, fluoroquinolones (ciprofloxacin, moxifloxacin, gatifloxacin), aminoglycosides (gentamicin, tobramycin), erythromycin, cefazolin, oxacillin, and vancomycin were collected. RESULTS: Review of records yielded 20,180 conjunctival bacterial cultures, 60.1% of which were culture-positive. Of the culture-positive isolates, 76.6% were gram-positive and 23.4% were gram-negative pathogens. Staphylococcus aureus was the most common gram-positive pathogen isolated, and also the most commonly isolated pathogen overall. Haemophilus influenzae was the most common gram-negative pathogen. A significant increase in the percentage of methicillin-resistant Staphylococcus aureus (MRSA) was observed in the course of 11.5 years. The highest levels of antibiotic resistance were observed to tetracycline, erythromycin, and TMP/SMZ. Gram-positive isolates were least resistant to vancomycin, and gram-negative isolates were least resistant to imipenem. The lowest broad-spectrum antibiotic resistance was observed in the case of moxifloxacin, gatifloxacin, and aminoglycosides. CONCLUSION: Staphylococcus aureus is the most common pathogen in bacterial conjunctivitis. Conjunctival bacterial isolates demonstrated high levels of resistance to tetracycline, erythromycin and TMP/SMZ. Moxifloxacin and gatifloxacin appear to be currently the best choice for empirical broad-spectrum coverage. Vancomycin is the best antibiotic for MRSA coverage.

Taut internal limiting membrane causing diffuse diabetic macular edema after vitrectomy: clinicopathological correlation.

AIMS: To describe 2 cases of diffuse diabetic macular edema (DME) after diabetic vitrectomy caused by a taut internal limiting membrane (ILM), with clinicopathological correlation. METHODS: Interventional case series with immunohistochemical analysis. RESULTS: Two patients were referred for unresponsive diffuse DME after pars plana vitrectomy with removal of the posterior hyaloid. Clinically, a taut ILM was noted over the fovea, and its removal resulted in rapid and long-term resolution of the edema, confirmed by optical coherence tomography with visual acuity improvement. Histopathology with immunostaining revealed a segment of ILM with an inner monolayer of cytokeratin-positive (retinal pigment epithelial cells) and/or glial fibrillary acidic protein-positive cells with smooth muscle actin immunoreactivity. CONCLUSIONS: A taut ILM can cause diffuse DME after vitrectomy, and its removal can restore the normal foveal contour and improve visual acuity. Tangential tractional forces from contractile cells propagated across the fovea via the ILM appear to be the etiology.

Primary melanoma of the optic nerve in a patient with 16-year follow up.

Primary melanoma of the optic nerve is rare. Limited reports in the literature have been the subject of considerable controversy, as many of these melanomas have later been found to be metastatic disease or local extensions of a juxtapapillary choroidal melanoma. Moreover, these have often been reported in patients with a history of ocular or oculocutaneous pigmentary disorders. The authors present a case of primary melanoma of the optic nerve in a patient with no history of pigmentary disorder and 16 years of follow up.

Subtoxic levels hydrogen peroxide-induced production of interleukin-6 by retinal pigment epithelial cells.

PURPOSE: To study the effect of subtoxic levels of hydrogen peroxide (H(2)O(2)) on the expression and release of interleukin-6 (IL-6) by cultured retinal pigment epithelial (RPE) cells and to explore the relevant signal pathways. METHODS: Cultured human RPE cells were stimulated with various subtoxic concentrations of H(2)O(2) for different periods. Conditioned medium and cells were collected. IL-6 in the medium and IL-6 mRNA in the collected cells were measured using an IL-6 enzyme-linked immunosorbent assay kit and reverse transcriptase polymerase chain reaction, respectively. Nuclear factor-kappaB (NF-κB) in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinases (JNK) in cells cultured with and without H(2)O(2) were measured by NF-κB and MAPK enzyme-linked immunosorbent assay kits. Inhibitors of p38 (SB203580), ERK (UO1026), JNK (SP600125), and NF-κB (BAY11-7082) were added to the cultures before the addition of H(2)O(2) to test their effects(.) RESULTS: Subtoxic levels of H(2)O(2) (100 µM and less) increased the IL-6 mRNA level and the release of IL-6 protein by the cultured human RPE cells in a dose- and time-dependent manner. This was accompanied by an increase of NF-κB in nuclear extracts and phosphorylated p38 MAPK, ERK, and JNK in cell lysates, particularly in the p38 and NF-κB. The NF-κB inhibitor decreased the H(2)O(2)-induced expression of IL-6. The p38 inhibitor, but not the ERK or JNK inhibitor, completely abolished H(2)O(2)-induced expression of IL-6 by RPE cells. The p38 inhibitor also abolished the increase of NF-κB in nuclear extracts in cells treated with H(2)O(2). CONCLUSIONS: H(2)O(2) stimulated the production of IL-6, a key factor in the modulation of immune responses, inflammatory processes, and the occurrence of autoimmune diseases, which recently has been documented to be increased in age-related macular degeneration (AMD). This may be a molecular linkage for the oxidative stress and inflammatory/autoimmune reactions in AMD and may provide a novel target for the treatment of AMD.

Melanocytic nevi of the tarsal conjunctiva: clinicopathologic case series with review of literature.

PURPOSE: To describe 4 patients with histopathologically confirmed tarsal conjunctival nevi and to review the literature regarding nevi in this location. METHODS: Clinicopathologic series of 4 cases diagnosed at the New York Eye and Ear Infirmary between January 1990 and April 2009. PubMed was searched for reported cases of tarsal conjunctival nevi. RESULTS: Four patients (mean age 44 years, median 50 years, range 5-70 years) with tarsal conjunctival nevi were identified (3.4% of all histopathologically diagnosed conjunctival nevi). These lesions presented in adulthood (3 cases) and were associated with elevation/nodularity (3 cases), gray-brown coloration (3 cases), physician-documented growth (1 case), madarosis (1 case), and intrinsic vessels (1 case). Histopathology revealed combined nevi centered in the posterior lamella of the eyelid, predominantly in peri-Meibomian gland distribution. Review of the literature identified 10 previously reported cases of tarsal nevi with detailed clinicopathologic correlation in 3 of these patients. CONCLUSIONS: Tarsal conjunctival nevi are rare. Adult presentation; subjective and objective evidence of growth; and associated inflammation, vascularity, and eyelid margin changes may make clinical distinction of tarsal nevi from melanoma challenging. Biopsy, therefore, is prudent as histopathology alone allows documentation of the benign nature of these lesions.

Urinary 6-sulfatoxymelatonin level in age-related macular degeneration patients.

PURPOSE: Melatonin is a potent antioxidant and free radical scavenger. It has been reported that serum melatonin level is relevant to certain aging diseases. The purpose of this study was to investigate melatonin levels in age-related macular degeneration (AMD) patients by measurement of 6-sulfatoxymelatonin levels (aMT6s), the major metabolite of melatonin in urine, and compare it with a group of age- and gender-matched controls. METHODS: The first urine of the morning was collected from 43 AMD patients and 12 controls who did not have AMD. The level of aMT6s in specimens was measured by a commercial 6-sulfatoxymelatonin ELISA kit. The assay was performed by researchers, who were masked to the clinical information. To adjust for variation in the diluteness of urine, urinary creatinine level was measured and aMT6s levels were expressed as aMT6s/creatinine. RESULTS: The level of urinary aMT6s/creatinine (mean+/-SD) in AMD (6.24+/-3.45 ng aMT6s/mg creatinine) was significantly lower than that of the controls (10.40+/-4.51, p=0.0128). After adjustment for various factors (age, smoking, cancer, and coronary heart disease) that may influence the aMT6s level, the odds-ratio of urinary aMT6s comparing AMD patients to controls was 0.65 (95% confidence interval=0.48-0.88, p=0.0036), indicating that urinary aMT6s level in AMD patients was lower than in controls even after multivariate adjustment. CONCLUSIONS: Urinary aMT6s level in AMD patients was 40% lower than in age- and gender-matched controls. This difference between AMD patients and controls is present after adjustment for the factors of age, smoking, and histories of cancer and coronary heart disease. The significance of this result and the role of melatonin in the occurrence of AMD require further investigation.

Syringocystadenoma papilliferum of the eyelid.

PURPOSE: To describe 6 patients with syringocystadenoma papilliferum of the eyelid and to review the literature regarding this rare eyelid tumor. METHODS: Clinicopathologic series of 6 cases, diagnosed at the New York Eye and Ear Infirmary from 1990 to 2006. The PubMed database was searched for reported cases of syringocystadenoma papilliferum of the eyelid (keywords: syringocystadenoma, eyelid, apocrine, eccrine). RESULTS: Fourteen patients (6 from the current case series and 8 previously reported) with syringocystadenoma papilliferum of the eyelid were identified. Patient age ranged from 8 to 82 years (mean, 44.6 years). Most cases had a preoperative diagnosis of basal cell carcinoma or cyst. Histopathologic evaluation of excised lesions revealed proliferation of duct-like channels in the dermis. These channels were lined by nonkeratinizing epithelium and communicated with the epidermis. Papillary structures with plasma cell-rich stromal infiltrate protruded in the cystic invaginations. Nine lesions (64%) were associated with apocrine, eccrine, or sebaceous tumors or malformations. None of the lesions was associated with a malignant neoplasm. One lesion recurred after incomplete excision. None of the completely excised lesions recurred. CONCLUSIONS: Syringocystadenoma papilliferum can rarely affect eyelid skin. This lesion is frequently clinically misdiagnosed as basal cell carcinoma or cyst. Although syringocystadenoma papilliferum of the eyelid can be associated with other benign lesions, no malignant transformation or association with malignant neoplasms has been reported. The evidence suggests that this tumor should be managed with conservative complete excision.

Primary typical carcinoid tumor of the eyelid.

A 70-year-old woman presented with a slow-growing right lower eyelid lesion. Histopathologic and immunohistochemical evaluation of an excisional biopsy revealed a neuroendocrine neoplasm, consistent with a typical carcinoid tumor. Systemic investigation for occult visceral primary tumor was negative. Re-excision of the lesion for free surgical margins was performed. Eight months later, the patient remains well with no evidence of other primary malignancy or metastatic disease.

Subepidermal calcified nodules of the eyelid.

Subepidermal calcified nodule uncommonly involves the eyelid, and the authors report their experience with 9 cases of this entity. Most lesions appeared as solitary, raised, tan, or white nodules on the upper eyelid or medial canthal skin of healthy, young patients. The diagnosis was not suspected in any of the patients. The most common preoperative diagnosis was a "cyst." Excisional biopsy was performed in all cases and was curative with the exception of one recurrence. Histopathologic evaluation showed basophilic deposits beneath acanthotic and papillomatous epidermis on hematoxylin and eosin-stained preparations. The deposits stained with von Kossa's stain for calcium and were surrounded by foreign body reaction. Ophthalmologists should be aware that subepidermal calcified nodule is a benign lesion that can occur in the eyelid skin.

Population-based incidence of conjunctival melanoma in various races and ethnic groups and comparison with other melanomas.

PURPOSE: To investigate racial and ethnic differences in the incidence of conjunctival melanoma in a large population-based study. DESIGN: Observational cross-sectional study. METHODS: Using data from 1992 through 2003 provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, we calculated age-adjusted incidence rates of conjunctival melanoma in various racial and ethnic groups (Black, American Indian, Asian and Pacific Islander, Hispanic, and non-Hispanic White). In addition, we calculated the standard incidence ratios (risk ratios) and 95% confidence intervals to describe the differences within these racial and ethnic groups. RESULTS: From 1992 through 2003, there were a total of 168 conjunctival melanomas diagnosed in 13 SEER registries with known racial and ethnic groups. The annual age-adjusted incidence rates (per million population) of conjunctival melanoma was 0.18 (Blacks), 0.17 (American Indians), 0.15 (Asians), 0.33 (Hispanics), and 0.49 (non-Hispanic Whites). The difference in the incidence of conjunctival melanoma between Whites and Blacks or Asians was statistically significant, but was not significant between Blacks and Asians. CONCLUSIONS: The overall White-to-Black incidence ratio in conjunctival melanoma was 2.6:1, which is much less than that of uveal melanoma (18:1) and cutaneous melanoma (13:1 to 26:1), but is similar to that of mucosal melanoma (2.2:1 to 2.3:1). The cause and significance of this difference of racial and ethnic incidence in various melanomas are discussed.

Subretinal hemorrhage masquerading as a hemorrhagic choroidal detachment in a case of nonaccidental trauma.

Retinal hemorrhages are the most commonly reported ocular findings in nonaccidental trauma in children. Other reported ocular findings include perimacular folds, traumatic retinoschisis, choroidal hemorrhages, and retinal detachments. We report the clinical and pathologic findings in a case of a 10-month-old boy who sustained nonaccidental trauma and whose clinical presentation was characteristic of a hemorrhagic choroidal detachment. Postmortem examination revealed a large subretinal hemorrhage, with no evidence of choroidal hemorrhage.

Uveal melanocytes do not respond to or express receptors for alpha-melanocyte-stimulating hormone.

PURPOSE: Whereas cutaneous pigmentation increases after exposure to ultraviolet (UV) irradiation, ocular pigmentation does not. This study was designed to examine the evidence that alpha-melanocyte-stimulating hormone (alpha-MSH), which is thought to be the mediator of UV response in the skin, has any role to play in uveal melanocytes. METHODS: Human uveal melanocytes derived from the choroid and the iris were cultivated by using eyes harvested from adult cadaveric donors and were assessed by Northern blot analysis for growth and melanogenic response to alpha-MSH and expression of the receptor for alpha-MSH (MC1-R). In addition, expression of alpha-MSH was evaluated in ocular tissue by immunocytochemistry. RESULTS: Uveal melanocytes, unlike cutaneous melanocytes in vitro, exhibited no stimulation of proliferation in response to alpha-MSH at dosages ranging from 0.1 to 100 muM. In addition, tyrosine hydroxylase, DOPA oxidase, and protein levels for tyrosinase, TRP-1, and TRP-2 were not influenced by alpha-MSH. Associated with the lack of alpha-MSH response in cultured uveal melanocytes was the absence of expression of the receptor for alpha-MSH (MC1-R), as assessed by Northern blot analysis. Also in contrast to the skin, pigmented ocular tissue lacked expression of the alpha-MSH ligand, as assessed by immunocytochemistry. CONCLUSIONS: In conclusion, ocular pigmentation does not appear to be regulated by melanocyte stimulating hormone.

Latitude and incidence of ocular melanoma.

We investigated the associations between latitude and the incidence of two different types of ocular melanoma, external ocular melanoma (exposed to sunlight) and internal melanoma (not exposed to sunlight), separately. Using 1992-2002 data from the Surveillance, Epidemiology, and End Results (SEER) Program of National Cancer Institute, we identified 2142 ocular melanoma cases in non-Hispanic whites, and then regressed the incidences of various types of ocular melanomas with latitude. Our analysis indicated that the higher the latitude (away from the equator, the less sun exposure), the lower the risk of external ocular melanoma (eyelid and conjunctival melanomas) among non-Hispanic whites (P for trend = 0.018). The incidence increased 2.48 fold from 47-48 degrees to 20-22 degrees. This trend is very similar to that of skin melanoma. The incidence of internal ocular melanoma (uveal melanoma) increased significantly with increasing latitudes (the less sun exposure, P for trend < 0.0001), it increased 4.91 fold from 20-22 degrees to 47-48 degrees. The latitudinal patterns of ocular melanomas may reflect the dual effects of sunlight exposure, i.e. a mutagenic effect of direct solar radiation on external ocular melanomas and a protective effect for internal uveal melanoma, which is similar to the sun radiation protective effects for various internal malignant tumors that are not exposed to the sunlight.

Fungal keratitis at the new york eye and ear infirmary.

INTRODUCTION: This study was designed to review the clinical experience at our institution with fungal keratitis during a 16-year period. MATERIALS AND METHODS: A review of the clinical and microbiology records of the New York Eye and Infirmary identified 61cases of fungal keratitis in 57 patients between January 1, 1987 and June 1, 2003. The medical records of all patients were retrospectively reviewed to better delineate patient demographics, risk factors, etiologic organisms, treatment, and outcomes. RESULTS: A total of 5083 positive corneal cultures were recorded'from January 1, 1987 to June 1, 2003. Sixty-one eyes in 57 patients (37 women) were positive for fungus (1.2%). Three'patients had bilateral simultaneous infections. Candida albicans accounted for 29 of 61 cases (48%). Human immunodeficiency virus (HIV) seropositivity (15 eyes), chronic ocular surface disease (14 eyes), and trauma (7 eyes) were the most commonly associated risk factors. CONCLUSIONS: Our experience with fungal keratitis in the northeastern United States appears to be different than those reported from other areas of the United States. Serologic positivity for HIV and chronic ocular surface disease were the most common associated risk factors followed by trauma, herpes simplex keratitis, and contact lens use. Candida species predominated, whereas filamentous fungi were uncommon.