Search

Objective: To analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication., Design: Retrospective case-control study., Subjects: Patients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea., Methods: Targeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features., Main Outcome Measures: Presence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence., Results: Hotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized., Conclusions: In this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions., (Published by Elsevier Inc.)

Purpose: To present a unique case of polypoidal choroidal vasculopathy presenting as a blind, painful eye with a suspected intraocular mass, and to correlate clinical findings with histopathologic studies., Methods: Clinical case report and literature review., Results: A 58-year-old Vietnamese man presented with a blind, painful eye with concern for an intraocular mass. B-scan ultrasonography showed massive intraocular hemorrhage and could not rule out a tumor. The patient underwent enucleation and the histopathologic findings were consistent with polypoidal choroidal vasculopathy., Conclusion: Polypoidal choroidal vasculopathy can present with dense vitreous hemorrhage and may masquerade as an intraocular mass. It can progress rapidly and lead to profound, irreversible vision loss. A diagnosis of polypoidal choroidal vasculopathy should be considered in patients of African or East Asian origin presenting with vitreous hemorrhage.

The authors report a case of papillary cystadenocarcinoma of the lacrimal gland after irradiation for bilateral retinoblastoma. A 32-year-old man with a history of bilateral retinoblastoma, diagnosed shortly after birth, was treated with enucleation of the OS and a single session of radiation to the OD. Over 30 years later, he presented with an orbital mass of the right lacrimal gland that on biopsy demonstrated papillary cystadenocarcinoma.

Purpose: To study retinal structure in choroideremia patients and carriers using high-resolution imaging techniques., Methods: Subjects from four families (six female carriers and five affected males) with choroideremia (CHM) were characterized with best-corrected visual acuity (BCVA), kinetic and static perimetry, full-field electroretinography, and fundus autofluorescence (FAF). High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT). Coding regions of the CHM gene were sequenced., Results: Molecular analysis of the CHM gene identified a deletion of exons 9 to 15 in family A, a splice site mutation at position 79+1 of exon 1 in family B, deletion of exons 6 to 8 in family C, and a substitution at position 106 causing a premature stop in family D. BCVA ranged from 20/16 to 20/63 in carriers and from 20/25 to 5/63 in affected males. FAF showed abnormalities in all subjects. SD-OCT showed outer retinal layer loss, outer retinal tubulations at the margin of outer retinal loss, and inner retinal microcysts. Patchy cone loss was present in two symptomatic carriers. In two affected males, cone mosaics were disrupted with increased cone spacing near the fovea but more normal cone spacing near the edge of atrophy., Conclusions: High-resolution retinal images in CHM carriers and affected males demonstrated RPE and photoreceptor cell degeneration. As both RPE and photoreceptor cells were affected, these cell types may degenerate simultaneously in CHM. These findings provide insight into the effect of CHM mutations on macular retinal structure, with implications for the development of treatments for CHM. (ClinicalTrials.gov number, NCT00254605.).

Retinoinvasive uveal melanoma demonstrates prominent diffuse retinal and optic nerve invasion, with little or no involvement of the adjacent choroid. Prior studies have advanced hypotheses on the potential role of molecular and cellular interactions in the pathogenesis of retinoinvasiveness and neuroinvasiveness, but the precise molecular events are not known. Here, we investigate the role of neutrotrophic factors in the pathogenesis of retinoinvasive uveal melanoma. The records of three ophthalmic pathology departments (The New York Eye and Ear Infirmary, Wills Eye Institute, and University of California San Francisco) were searched to identify all cases of retinoinvasive uveal melanoma, yielding four eyes (all previously irradiated). Eight eyes with nonretinoinvasive melanomas (four irradiated and four nonirradiated) were randomly selected as controls. All enucleated eyes were examined histopathologically and immunohistochemically for the expression of neurotrophic factor receptors [Pan-Trk, p75 neurotrophin receptor (p75(NTR) and ciliary neurotrophic factor receptor-α]. Histopathologic features were similar in both retinoinvasive and control melanomas with regard to choroidal tumor location and size, neovascular glaucoma, and cell type. The eyes with retinoinvasive melanoma showed diffuse retinal invasion beyond the choroidal tumor (n=4) and prelaminar (n=1) and retrolaminar (n=2) optic nerve invasion. The control melanomas showed focal retinal invasion over the tumor apices (n=6) and prelaminar optic nerve invasion (n=1). Nonirradiated melanomas demonstrated no trace immunoreactivity for neurotrophic factor receptors, whereas irradiated melanomas showed more prominent (trace to moderate) immunoreactivity. When controlled for irradiation, no difference in immunoreactivity for neurotrophin receptors nor tumor duration was observed between retinoinvasive and nonretinoinvasive melanomas. This study failed to demonstrate a direct causation between the expression of neurotrophin receptors and a retinoinvasive uveal melanoma growth pattern.

Coccidioidomycosis can simulate an intraocular neoplasm. We reviewed a case report of a 10-year-old girl who was referred with an intraocular tumour. This tumour consisted of a coccidioidomycosis infection in the eye. The eye was blind and painful so it was removed.

Bacterial entry into the vitreous cavity via inadvertent scleral perforation is one postulated mechanism for poststrabismus surgery endophthalmitis. In a review of 746 cases, we identified 2 pediatric enucleation specimens related to complications of strabismus surgery. In both cases, the patients developed postoperative endophthalmitis and no light perception vision, and the eyes were enucleated when they became phthisical or painful. In both submitted cases, pathology showed a thick band of scar tissue emanating focally from the sclera into the vitreous. Although no needle tracts were visualized, pathological findings were consistent with scleral perforation., (Copyright © 2011 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Objective: To evaluate discordant clinical and pathological diagnoses leading to pediatric enucleations over time., Methods: All pathology reports of pediatric enucleation specimens (subjects aged 0 to 18 years) from 1960 to 2008 were reviewed. Specimens with discordant clinical and pathologic diagnoses were further analyzed. Formalin-fixed, paraffin-embedded sections of enucleated eyes of any misdiagnosed cases were reevaluated., Results: Of 729 pediatric patients (746 eyes) who had enucleation from 1960 to 2008, 29 patients (4.0%) and 30 eyes (4.0%) had discordant clinical and pathological diagnoses. The misdiagnosis enucleation rate decreased with each respective decade studied, with the highest rate of 6.5% (18 of 276 eyes) in the 1960s and no misdiagnoses from 1990 to 2008. Of the 369 eyes enucleated for the clinical indication of malignancy, 22 eyes (6.0%) were misdiagnosed in that no evidence of malignancy was found on histopathological examination. Of the 377 eyes enucleated for benign clinical indications, 7 cases (1.9%) were found to be malignant by histopathology., Conclusions: Misdiagnoses leading to pediatric enucleation have decreased during the past 5 decades, likely owing to improved diagnostic techniques. Benign and malignant intraocular conditions can simulate each other, especially retinoblastoma, Coats disease, nematode and bacterial endophthalmitis, panuveitis, and persistent hyperplastic primary vitreous.

Purpose: To evaluate diagnoses leading to enucleations in the pediatric age group over time., Methods: All pathology reports of enucleation specimens at the University of California-San Francisco eye pathology laboratory from children (ages 0 to 18 years) from 1960 to 2008 were reviewed. The main outcome measures were the frequency of pediatric enucleation specimens in each diagnostic category as compared with total pathological laboratory volume over time, and the age and gender distribution of histopathological diagnostic categories over time., Results: Specimens of 746 eyes from 729 pediatric patients were analyzed. Pediatric enucleated eyes constituted 2.7% of all specimens received at the pathology laboratory. The overall frequency of pediatric enucleation specimens did not change over time. Retinoblastoma specimens increased by a factor of 2.9 over time (p < 0.0001). The increase in retinoblastoma was offset by a decrease in nonretinoblastoma enucleations, which decreased by a factor of 3.8 between the 1960s and 2000s (p < 0.0001), driven by a decrease in enucleations caused by trauma (p < 0.0001). Beginning in the 1980s, pediatric enucleations caused by nonrhegmatogenous retinal detachment, nematode and non-nematode endophthalmitis, and congenital glaucoma decreased significantly. Retinoblastoma was the most common diagnosis overall (45%), in girls (60%), and in ages <5 years (78%). Trauma was the second most common diagnosis (32%) and the most common in boys (42%) and in children ages 6-12 (58%) and 13-18 (72%) years., Conclusions: A decrease in pediatric nonretinoblastoma enucleations was observed over time, possibly attributable to better diagnostic capabilities, surgical techniques, and public health interventions. The increase in retinoblastoma enucleations over time was likely due to the result of institutional referral bias., (Copyright (c) 2010 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

The redesign of azamacrocyclic CXCR4 chemokine receptor antagonists resulted in the discovery of novel, small molecule, orally bioavailable compounds that retained T-tropic (CXCR4 using, X4) anti-HIV-1 activity. A structure-activity relationship (SAR) was determined on the basis of the inhibition of replication of X4 HIV-1 NL4.3 in MT-4 cells. As a result of lead optimization, we identified (S)-N'-((1H-benzo[d]imidazol-2-yl)methyl)-N'-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine (AMD070) 2 as a potent and selective antagonist of CXCR4 with an IC(50) value of 13 nM in a CXCR4 125I-SDF inhibition binding assay. Compound 2 inhibited the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs with an IC(50) of 2 and 26 nM, respectively, while remaining noncytotoxic to cells at concentrations exceeding 23 microM. The pharmacokinetics of 2 was evaluated in rat and dog, and good oral bioavailability was observed in both species. This compound represents the first small molecule orally bioavailable CXCR4 antagonist that was developed for the treatment of HIV-1 infection.

Purpose: The purpose of this study was to report the occurrence of crystalline keratopathy and of orbital infiltrative disease resulting from crystal-storing histiocytosis (CSH) in a patient with monoclonal gammopathy of undetermined significance., Methods: The authors conducted a review of a medical record and immunohistopathologic studies., Results: A 66-year-old man presented with a 3-year history of unilateral progressive ptosis, proptosis, and external ophthalmoplegia. Magnetic resonance imaging showed orbital fat expansion and extraocular muscle thickening with gadolinium enhancement. The patient also had bilateral crystalline keratopathy and had undergone penetrating keratoplasty in one eye. The urine and serum showed elevated levels of immunoglobulin, but the bone marrow aspirate was normal. The systemic evaluation was consistent with monoclonal gammopathy of undetermined significance. An orbital fat biopsy revealed histiocytes engorged with lambda light chain crystals. The corneal stroma also showed positive immunostaining for lambda light chains. The patient was diagnosed with orbital CSH and with lambda light chain crystalline keratopathy., Conclusions: CSH is characterized by the accumulation of reactive histiocytes filled with immunoglobulin crystals in various tissues and is frequently associated with systemic hyperglobulinemic states. For unknown reasons, in this patient, a systemic immunologic disorder led to lambda light chain abnormalities with histiocyte infiltration of the orbit and corneal deposition. Although CSH is rare, it should be part of the differential diagnosis of orbital infiltrative disease with or without crystalline keratopathy.

The majority of mutations that cause isolated growth hormone deficiency type II are the result of aberrant splicing of transcripts encoding human growth hormone. Such mutations increase skipping of exon 3 and encode a 17.5-kDa protein that acts as a dominant negative to block secretion of full-length protein produced from unaffected alleles. Previously, we identified a splicing regulatory element in exon 3 (exonic splicing enhancer 2 (ESE2)), but we had not determined the molecular mechanism by which this element prevents exon skipping. Here, we show that two members of the serine/arginine-rich (SR) protein superfamily (ASF/SF2 and SC35) act antagonistically to regulate exon 3 splicing. ASF/SF2 activates exon 3 inclusion, but SC35, acting through a region just downstream of ESE2, can block such activation. These findings explain the disease-causing mechanism of a patient mutation in ESE2 that creates a functional SC35-binding site that then acts synergistically with the downstream SC35 site to produce pathological levels of exon 3 skipping. Although the precedent for SR proteins acting as repressors is established, this is the first example of a patient mutation that creates a site through which an SR protein represses splicing.

Background: Two cases of conjunctival carcinoma developed orbital invasion during treatment with topical medication., Methods: This was a retrospective study from a tertiary ophthalmic oncology unit, performed after informed consent was obtained. The main outcome measurement was orbital invasion., Results: Two patients treated with topical agents developed orbital invasion., Conclusion: While topical agents are important in treatment of conjunctival neoplasia, recurrence or deep invasion require careful monitoring.

A spontaneous dynamic kinetic resolution of 8-amino-5,6,7,8-tetrahydroquinoline 1 was observed in the presence of Candida antarctica Lipase B, in which a >60% yield of (R)-acetamide [(R)-2] was isolated from the racemic amine. The spontaneous formation of ketone 3, followed by a condensation/hydrolysis sequence with the remaining (S)-amine 1, via enamine 4, provides the necessary racemization pathway.

The inclusion of exons 2 and 3 of alpha-tropomyosin is governed through tissue-specific alternative splicing. These exons are mutually exclusive, with exon 2 included in smooth muscle cells and exon 3 included in nearly all other cell types. Several cis-acting sequences contribute to this splicing decision: the branchpoints and pyrimidine tracts upstream of both exons, UGC-repeat elements flanking exon 3, and a series of purine-rich enhancers in exon 2. Previous work showed that proteins rich in serine-arginine (SR) dipeptides act through the exon 2 enhancers, but the specific proteins responsible for such activation remained unknown. Here we show that a 35-kDa member of the SR protein family, 9G8, can activate the splicing of alpha-tropomyosin exon 2. Using RNA affinity chromatography and cross-linking competition assays, we also demonstrate that the heterogeneous nuclear ribonucleoproteins (hnRNPs) H and F bind to and compete for the same elements. Overexpression of hnRNPs H and F blocked 9G8-mediated splicing both in vivo and in vitro, and small interfering RNA-directed depletion of H and F led to an increase in exon 2 splicing. These data suggest that the activation of exon 2 is dependent on the antagonistic activities of 9G8 and hnRNPs H and F.

Purpose: To report a case of metaplastic squamous epithelial downgrowth after cataract surgery., Design: Interventional case report., Methods: Clinical, laboratory, and histologic findings are presented. Our study is in compliance with institutional review board guidelines., Results: A 76-year-old man developed anterior chamber inflammation five months after uncomplicated clear corneal cataract surgery. Despite antimicrobial and anti-inflammatory therapies, the inflammation persisted. An extensive examination failed to demonstrate an infectious etiology or lymphoma. Subsequently, the patient developed an incipient limbal lesion and iris mass. Immunostaining of a biopsy specimen from the iris mass indicated an epithelial-derived tumor. The prephthisical and painful eye was enucleated; histopathology of the globe revealed a contiguous lesion extending from the limbal mass to the iris tumor through the surgical incision site, a finding consistent with metaplastic squamous epithelial downgrowth. Systemic evaluation was negative., Conclusions: After intraocular surgery, metaplastic epithelial downgrowth may occur as a consequence of occult ocular surface squamous neoplasia and masquerade as chronic inflammation; clinicians should be aware of this rare complication.

Purpose: To report the microbiological, clinical, and pathological characteristics of community-associated methicillin-resistant Staphylococcus aureus (CAMRSA) infections of the eye and orbit., Design: Prospective case series., Participants: Nine patients with CAMRSA infections of the eye and orbit were identified during a 6-month period at 2 tertiary care hospitals in San Francisco., Methods: Case identification was by prospective case selection and retrospective laboratory review of 549 MRSA cultures collected in the 2 hospitals. Ophthalmic microbial isolates were analyzed by pulsed-field gel electrophoresis and compared with a control CAMRSA clone (USA300). Clinical characteristics of patients infected with CAMRSA were reviewed, and all surgical specimens underwent pathological examination., Main Outcome Measures: Pulsed-field gel electrophoresis banding patterns of MRSA isolates, antibiotic sensitivity profiles, patient demographics, systemic and ocular complications of infection, and posttreatment visual acuities., Results: Nine ophthalmic isolates were CAMRSA clone USA300. The infections included orbital cellulitis, endogenous endophthalmitis, panophthalmitis, lid abscesses, and septic venous thrombosis. Patients were treated with trimethoprim-sulfamethoxazole, rifampin, clindamycin, or vancomycin based on microbial sensitivity studies and severity of infection. Eight of the 9 patients had no history of hospitalization. Seven patients required hospitalization, 3 required surgery, and an additional 4 required invasive procedures. Eight patients had good visual outcomes, but 1 deteriorated to no light perception. Pathological analyses showed extensive necrosis in eyelid and orbital specimens, and disorganized atrophy bulbi in an enucleated eye., Conclusion: The USA300 CAMRSA clone, which carries Panton-Valentine leukocidin genes, can cause aggressive infections of the eye and orbit in hospital-naive patients. Treatment of infections often required debridement of necrotic tissues in addition to non-beta-lactam class antibiotics. In communities where CAMRSA is prevalent, ophthalmologists should obtain microbial cultures and sensitivity studies to help guide antibiotic therapy for severe ophthalmic infections.

Aims: To delineate the diagnostic accuracy of fine needle biopsy in iris ring melanoma and determine the tumour related mortality of this neoplasm., Methods: A retrospective analysis of 22 patients with iris melanomas that involve the entire 360 degrees of the anterior chamber angle., Results: Iris ring melanomas were correctly diagnosed in all cases. In 11 of 16 cases (69%) a fine needle biopsy performed 180 degrees away from the main mass was positive for an iris ring melanoma. The tumour related mortality in iris ring melanoma cases was four of 22 patients (18%). Actuarial survival analysis showed a 10 year mortality (Kaplan-Meier) of 15%., Conclusion: A fine needle aspiration biopsy can be used to diagnose an iris ring melanoma. Iris ring melanomas have significant mortality compared with focal tumours.

Purpose: To report a case of bilateral endogenous fungal endophthalmitis resulting from disseminated Scedosporium prolificans., Design: Observational case report., Methods: A 56-year-old woman with cystic fibrosis status post dual lung transplantation on chronic immunosuppressive therapy presented with acute graft rejection. Cultures of bronchial brushings revealed S. prolificans. Three weeks after admission, the patient noted increased blurriness and a central scotoma in her right eye. Dilated fundus examination revealed profound vitritis in the right eye with hemorrhagic retinitis involving the macula. A peripheral, yellow choroidal infiltrate with overlying retinitis and localized vitritis was present in the left eye., Results: Intravitreal antibiotics were initiated, and vitreous cultures revealed S. prolificans. The patient ultimately succumbed to her disseminated disease. Pathologic examination of the eyes confirmed bilateral endogenous fungal endophthalmitis., Conclusion: S. prolificans is an opportunistic infection resistant to standard antifungal therapy that can result in endogenous endophthalmitis in immunocompromised individuals.

Purpose: To determine whether an increase (or progression) in the degree of malignancy according to cytologic or histopathologic criteria corresponded with failure of intraocular melanoma control., Design: Retrospective case control study from a single institution., Methods: Uveal melanoma patients had either fine-needle aspiration biopsy followed by irradiation and later enucleation or an eyewall resection followed by enucleation. The observation procedures were serial histology or cytopathology and histology, reanalyzed in a masked manner. The main outcome measures were change in the predominant tumor cell type, local tumor control, and metastases., Results: There was not a significant correlation between a change in melanoma cell type and failure to control intraocular melanoma. Similarly, the latency between treatment and enucleation was actually less (but not statistically so) in tumors that showed no increase in melanoma malignancy cell type compared with those that had a more malignant cell type on serial examination., Conclusions: There was no correlation between a change to more a malignant cell type and local control failure in patients treated either with radiation or eyewall resection for uveal melanoma.

Purpose: To describe an American family with lattice corneal dystrophy type I, which associates with a novel mutation, Leu569Arg, of the TGFBI (BIGH3) gene., Design: Experimental study., Methods: Genomic DNA was extracted from buccal epithelial cells of four affected members of an American family with lattice corneal dystrophy type I. All 17 exons of the TGFBI gene were evaluated by PCR amplification and direct sequencing. Clinical and histologic data were also collected., Results: Three generations of this family have been positively diagnosed with lattice corneal dystrophy, indicating autosomal dominant inheritance. We identified a heterozygous point mutation that associates with the disease phenotype. The single base-pair substitution (T1753G) results in an amino acid substitution (Leu569Arg) in exon 13 of the TGFBI gene., Conclusions: Substitution of arginine for leucine at position 569 of the TGFBI gene results in a form of lattice corneal dystrophy that is phenotypically similar to other genetically distinct forms of type I disease. This is the first report of disease correlated with changes in exon 13 of the TGFBI gene.

Aim: To review the ocular retention rates, visual results, and metastases in uveal tumours managed with eye wall resection techniques., Methods: This was a retrospective analysis of consecutive local uveal tumour resections performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data were performed., Results: 138 eyes were scheduled for eye wall resection surgery. The mean age was 52 years (range 11-86 years). Tumours involved predominantly the iris in 14 cases, iris-ciliary body in 57, ciliary body alone in 18 patients, and in 49 cases the choroid was involved (ciliochoroidal, iris-ciliary body-choroid, or choroid). 125 eyes harboured melanomas; posterior tumours were more likely to have epithelioid cells (p<0.05). The mean follow up was 6 years. The mean clock hours in iris and iris-ciliary body tumours was 3.5. In tumours that involved the choroid the mean largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138 (76%) eyes were retained. Histological assessment of surgical margins did not correlate evidence of tumour in enucleated eyes or metastatic disease. Surgical margins of more anterior tumours were more likely to be clear on histological evaluation (p<0.05). Approximately 53% of retained eyes had a final visual acuity of > or =20/40; visual results were significantly better in more anteriorly located tumours (p<0.05). All retained iris tumour cases had > or =20/40 final visual acuity. In tumours that involved the choroid nine of 31 retained eyes kept that level of visual acuity. Eight patients developed metastases; all metastatic events developed in patients with tumours that involved the choroid, and seven of eight were mixed cell melanomas., Conclusions: 76% of eyes were retained and 53% of these had a final visual acuity of > or =20/40. Only 7% of uveal melanoma patients developed metastatic disease with a mean follow up of 6 years. Survival did not appear to be compromised with eye wall resection and in very thick, more posterior melanomas it appeared that ocular retention and visual results were better than with radiation alone.

Purpose: To review the ocular retention rates, visual results, and metastases in uveal tumors managed with eye-wall resection techniques., Methods: This was a retrospective analysis of uveal tumors selected for eye-wall resection with the surgical procedures performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data was performed., Results: A total of 132 eyes were scheduled for eye-wall resection surgery. Mean patient age was 52 years (range, 11 to 86 years). Tumors involved the iris alone in 17 cases, the iris-ciliary body in 53, the ciliary body alone in 16, and the choroid (ciliochoroidal, iris-ciliary body-choroid, or choroid) in 46 cases. A total of 114 eyes harbored melanomas; tumors located more posteriorly were more likely to have epithelioid cells (P < .05). Mean follow-up was 6 years. Mean number of clock hours in iris and iris-ciliary body tumors was 3.5. In tumors that involved the choroid, the mean largest diameter was 12.6 mm and the mean thickness was 8.2 mm. Ninety-three (70%) of 132 eyes were retained. Histologic assessment of surgical margins did not correlate with either evidence of tumor in enucleated eyes or metastatic disease. Surgical margins of tumors located more anteriorly were more likely to be clear on histologic evaluation (P < .05). Approximately 56% of retained eyes had a final visual acuity of 20/40 or better; visual results were significantly better in tumors located more anteriorly (P < .05). All retained eyes with iris tumors had a final visual acuity of 20/40 or better. In tumors that involved the choroid, 8 of 25 retained eyes kept visual acuity of 20/40 or better. Metastases developed in 8 patients; all metastatic events developed in patients with tumors that involved the choroid, and 7 of 8 were mixed cell melanomas., Conclusions: Seventy percent of eyes were retained, and 56% of these had a final visual acuity of 20/40 or better. Only 7% of patients with uveal melanoma developed metastatic disease (mean follow-up, 6 years). Survival did not appear to be compromised with eye-wall resection, and in very thick melanomas located more posteriorly, ocular retention and visual results appeared to be better than that attained with radiation alone.

Objective: To report the clinical and histologic features of combined nevi of the conjunctiva, a type of nevus that is not uncommon in the skin but rarely has been reported in the conjunctiva., Methods: Conjunctival nevi and melanomas in the files of the University of California at San Francisco Eye Pathology Laboratory from 1984 to 1999 were reviewed for the presence of features of both standard nevocytic nevi and blue nevi. Clinical histories and, when available, clinical photographs were obtained., Results: Thirty combined nevi were discovered between 1984 and 1999. One case before 1984 had been incorrectly diagnosed as a junctional nevus. The dendritic and spindle-shaped blue nevus cells had been overlooked because they were not recognized as distinct from the standard nevocytic nevus cells. The recognition of blue as well as a brown color, a deep as well as a superficial component in the lesion, or a history of pigmentation since birth may help to establish the correct clinical diagnosis and prevent an unnecessarily deep surgical resection. Although growth of the lesion or "satellites" in some may favor a clinical diagnosis of melanoma, no lesions in this series were malignant., Conclusion: Despite a paucity of reports of combined nevi of the conjunctiva in the medical literature, this type of nevus, a combination of a nevocytic and a blue nevus, is common and has been overlooked in the past.

Purpose: Hydroxyapatite (HA) spheres used to replace volume after an enucleation are often wrapped with autologous tissue before orbital implantation. Man-made materials are less expensive and pose no risk for viral transmission. The use of expanded polytetrafluoroethylene (ePTFE) to wrap HA spheres was evaluated., Methods: The medical records of 2 consecutive patients who underwent uncomplicated implantation of an HA sphere wrapped in ePTFE were reviewed., Results: An unusual reaction to the ePTFE material that was nonresponsive to topical or systemic antibiotic therapy developed in these 2 patients. Eventual wound erosion and bacterial infection of the implant necessitated its removal., Conclusions: Although well tolerated in other surgeries, ePTFE, when used to wrap HA spheres and placed into the orbit, may cause persistent conjunctival discharge, pyogenic granuloma formation, and eventual wound erosion. Therefore, the use of this material to wrap HA spheres is not recommended.

Purpose: To report the clinical and histologic features of combined nevi of the conjunctiva, a type of nevus that is not uncommon in the skin but has rarely been reported in the conjunctiva., Methods: Conjunctival nevi and melanomas from the files of the University of California, San Francisco, eye pathology laboratory were reviewed from 1984 to 1999 for the presence of features of both standard nevocytic nevi and blue nevi. Clinical histories and, when available, clinical photographs were obtained., Results: Thirty-one combined nevi were discovered during the 15-year period between 1984 and 1999. One case before 1984 had been incorrectly diagnosed as a junctional nevus. The dendritic and spindle-shaped blue nevus cells had been overlooked because they were not recognized as distinct from the standard nevocytic nevus cells. The recognition of a blue as well as a brown color, a deep as well as a superficial component in the lesion, or a history of pigmentation since birth may help to establish the correct clinical diagnosis and prevent an unnecessarily deep surgical resection. Although growth of the lesion or "satellites" in some patients may favor a clinical diagnosis of melanoma, none of the lesions in this series were malignant., Conclusion: Despite a paucity of reports of combined nevi of the conjunctiva in the medical literature, this type of nevus--a combination of a nevocytic and a blue nevus--is common and has been overlooked in the past.

Purpose: To report a 6-year-old boy who had benign mixed tumor (pleomorphic adenoma) of the lacrimal gland., Methods: A 6-year-old boy was referred for evaluation of a lacrimal fossa mass. We performed a lateral orbitotomy and excised the mass., Results: Histopathologic evaluation of the excised orbital mass disclosed a benign mixed tumor (pleomorphic adenoma) of the lacrimal gland., Conclusion: Benign mixed tumors (pleomorphic adenomas) of the lacrimal gland are rare in children. However, they must be considered in the differential diagnosis of pediatric orbital masses because of the prognostic importance of removing a pleomorphic adenoma with the capsule intact.

Purpose: To illustrate some management problems with pigmented iris tumors., Methods: This is a retrospective analysis of 234 iris tumors managed by one of the authors. Five patients were selected whose clinical course and pathologic data illustrate diagnostic problems that can occur with these tumors., Results: In the patients described, diagnostic problems were noted. In two patients, glaucoma specialists were unable to correctly diagnose an iris melanoma before filtration. One patient had a 3-clock-hour iris biopsy that was not diagnostic for malignancy, yet the enucleated eye showed melanoma. One patient with a clinically stable iris tumor had a mixed-cell melanoma., Conclusions: Most iris-pigmented tumors have a benign disease course. In some case, despite little clinical evidence of disease activity or progression, a melanoma, often with epithelioid cells, may be present and neither a fine-needle nor an open biopsy is always diagnostic.

Background: Although cytomegalovirus (CMV) infection of the retina and brain is common in patients with acquired immunodeficiency syndrome (AIDS), it is exceedingly rare in patients with immunodeficiencies due to other causes. This is the first report on ocular and cerebral histopathology of disseminated CMV in a child with severe combined immunodeficiency syndrome (SCID)., Methods: The authors examined by routine histopathologic methods the eyes of a 2-year-old white boy with SCID and bilateral CMV retinitis who died after failure of a third attempt at allogeneic bone marrow transplantation (BMT)., Results: Cytomegalovirus inclusions were found in the necrotic retinal remnants, in the hyperplastic and scarred retinal pigment epithelium, and bilaterally in the optic nerves. There were infiltrates of macrophages in response to the infection or the infused silicon, but no lymphoid infiltrates. Cytomegalovirus inclusions also were found in brain tissue., Conclusion: The histologic features resembled those of CMV retinitis and optic neuritis in AIDS.

A patient with recurrent squamous cell carcinoma of the conjunctiva was referred with 20/20 vision in an eye with obvious intraocular extension. A modified iridocyclochoroidectomy was performed and the tumour was removed. Three and a half years later the patient's vision is 20/30 and there is no recurrence. This is the first case in which an eye has been successfully salvaged with documented intraocular squamous cell carcinoma of the conjunctiva.

A number of approaches are being investigated to increase the prognostic accuracy for uveal melanoma patients; the standard deviation of nucleolar area measurements and the DNA content appear to correlate better with survival than do classic histologic parameters. The utility of performing cytomorphometric measurements on fine needle aspiration (FNA) biopsy samples was prospectively analyzed for 24 eyes containing uveal melanomas that were examined with both 25-gauge FNA biopsy and standard histologic techniques. "Masked" analysis of the cellular composition of the 24 cases showed the presence or absence of epithelioid cells to be accurately predicted on the FNA samples in all cases. Image analysis cytomorphometric measurements of nucleolar area showed marked variability (with r less than 0.4) when FNA and histologic samples from the same case were compared. The relationship between these measurements was affected by cell type, sampling, specimen processing and investigator experience.

In three cases of benign pigmented lesions (one melanocytoma and two pigment epithelial adenomas) there was evidence of tumor growth and the lesions were referred to us as uveal melanomas. The fine needle aspiration biopsy specimens were correctly interpreted in the operating room as being benign tumors. The pigment granules in these benign pigmented lesions are much larger than are observed in uveal melanomas. When they were visible through the heavy pigmentation, the cellular detail appeared benign. In two cases the tumors were successfully resected with cyclochroidectomy techniques and the visual outcome was good. The third eye was studied after it had been removed at another institution. Fine needle aspiration biopsy can often differentiate a benign-simulating pigmented lesion from uveal melanoma.

A newly developed compact (40 kg), self-contained contact Neodymium:YAG laser produces high-peak, high-energy (800 mJ/pulse), short (1.0 millisecond) pulses with 1 to 3 pulses/exposure. Energy is delivered via a 320-microns cleaved quartz fiber optic probe. Cyclophotocoagulation was performed in five eyes of three medium-sized Dutch-pigmented rabbits. The eyes received exposures of 1 to 3 pulses/exposure. Energy delivered ranged from 100 to 800 mJ/pulse. Histopathology revealed ciliary body disruption and hemorrhage with no damage to overlying sclera. When used for transscleral cyclodiathermy in the rabbit, the laser created significant ciliary body disruption with minimal scleral injury.

A 50-year-old man with a history of systemic carcinoid had decreased right eye vision and a darkly pigmented cilio-choroidal mass. Results of ultrasonographic and fluorescein angiographic examinations were consistent with a malignant melanoma. Fine-needle aspiration biopsy of the lesion identified it as a carcinoid metastasis. The patient refused both radiation and enucleation; complete excision with a cyclochoroidectomy was performed. Histopathologic examination showed a carcinoid neoplasm covered by marked hyperplasia of the retinal pigment epithelium that produced the pigmented appearance of the lesion.

A chromium-sensitized, and thulium and holmium-doped YAG laser (THC:YAG laser) was used to create bilateral limbal sclerostomies in six Dutch pigmented rabbits. The laser is a long-pulsed (300 microseconds) [corrected], compact, self-contained, solid-state laser operating in the near infrared (2.1 microns). A 1-mm conjunctival stab incision was made 12 mm away from the sclerostomy site to allow entry of a specially designed 26-gauge (480 microns) optic probe that delivers energy at right angles to the long axis of the fiber. Probe insertion minimally disturbed the conjunctiva. Pulse energies of 60 to 150 mJ were used with a repetition rate of 5 pulses/s. Energy levels ranging from 1.35 to 6.6 J produced full-thickness sclerostomies. Histopathology showed a sharply defined perforating limbal wound at all energy levels. The overlying conjunctiva was intact, with swelling of the adjacent cornea. A peripheral iridectomy was intentionally created with the laser through the peripheral limbus, resulting in a sharply defined perforating tract through the iris/ciliary body. This technique may simplify filtering sclerostomy surgery, without anterior chamber instrumentation and with minimal conjunctival trauma.

A silicone tube is often passed through a fellow normal canaliculus in the treatment of a lacerated canaliculus in order to form a loop in the medial canthus and unite the ends of the tube in the nose. The histopathologic effects of the tube on the canaliculus and the constant frictional trauma caused by movement of the tube with blinking are not known. We intubated both normal and lacerated canaliculi of dogs to determine whether any damage occurred to the normal canaliculus and whether the inflammatory response following surgical repair of canalicular lacerations was prolonged or altered by the tube. We found no significant damage to the normal canaliculus and no increase in the surgical inflammation. Following the repair of a laceration, the canalicular epithelial layer healed along the silicone tube in spite of the constant frictional trauma. These findings support the safety of the use of the silicone tube in the treatment of canalicular disorders.

A child with nonrhegmatogenous retinal detachment associated with morning glory disc underwent first a vitrectomy and then, some months later, an optic nerve sheath fenestration. The latter procedure led to retinal reattachment. It also produced a biopsy specimen that confirmed the perineural herniation of poorly differentiated retinal tissue in this condition, similar to that in congenital pit of the optic nerve. It demonstrated continuity of the vitreous cavity with the perineural space, both histologically and by the fact that gas injected through the pars plana into the vitreous cavity bubbled out the window in the optic nerve sheath. The authors suggest that morning glory disc and optic pit share similar anatomic features, differing more in degree than in kind, and that the porous nature of the poorly differentiated tissue herniated around the optic nerve into the subarachnoid space in these conditions makes several sources of subretinal fluid possible.

We prospectively studied 51 patients with choroidal melanomas in a masked manner to determine the accuracy of clinical, ultrasound, and fluorescein diagnosis as well as the accuracy of tumor size measurements. In patients with clear media, clinical diagnosis was the most accurate means of detecting a choroidal melanoma. There was excellent correlation between clinical, ultrasound, and pathology measurements of tumor size. In small melanomas, clinical examination was the most accurate means of measuring tumor diameter and ultrasound the most accurate method of measuring tumor height. Even with a trained ocular oncologist, there was a significant variability in tumor measurements on serial ophthalmoscopic examinations.