Clear cell differentiation in choroidal melanoma. COMS report no. 8. Collaborative Ocular Melanoma Study Group

OBJECTIVE: To describe 2 enucleated eyes of patients enrolled in the Collaborative Ocular Melanoma Study that contained primary choroidal melanoma with clear cell features. METHODS: During a 9-year period, 1493 eyes enucleated as part of the Collaborative Ocular Melanoma Study routinely processed for histologic examination were evaluated by the pathology review committee (H.E.G, D.M.A, and W.R.G). Two eyes with unusual variants of choroidal melanoma were identified and immunostained for S100 protein and HMB 45. Portions of the tumors were processed for electron microscopic examination. RESULTS: Results of electron microscopic examination of both tumors displayed malignant melanoma (mixed cell type with many malignant cells with clear cytoplasm). The cytoplasm of the clear cells stained with periodic acid-Schiff and failed to stain when pretreated with diastase. Results of immunohistochemical stains in both tumors were positive for S100 protein and HMB 45 in the tumor cells. Results of electron microscopic examination showed that the cytoplasm of the clear cells contained scattered glycogen granules, premelanosomes, and melanosomes. CONCLUSION: These cases represent a clear cell variant of malignant melanoma of the choroid. This tumor should not be confused with metastatic clear cell carcinoma to the choroid.     

Communicating more effectively with the confused or demented patient

AIMS/BACKGROUND: Ocular cicatricial pemphigoid (OCP) can present with severe conjunctival inflammation that requires systemic immunosuppression to avoid serious ocular morbidity. This study aimed to assess the clinical response to cyclophosphamide and short term, high dose prednisolone in this group of patients. METHODS: A prospective, unmasked study assessed patients presenting with either 'severe' ocular inflammation (n = 4) or 'marked' or 'severe' ocular inflammation that had failed to respond to other systemic immunosuppression (n = 6). Nineteen inflamed eyes of 10 consecutive patients were enrolled. RESULTS: The ocular inflammation resolved in 15 eyes in a mean time of 2.4 months. Two eyes perforated despite treatment and one patient was unable to tolerate the medication. Progressive cicatrisation occurred in 21%. CONCLUSION: Cyclophosphamide and short term, high dose prednisolone are effective in severe inflammation caused by OCP but may not completely prevent cicatrisation.     

High-frequency radio-wave ablation of osteoid osteoma in the lumbar spine

This report describes a presumed choroidal granuloma with vitreous hemorrhage resembling choroidal melanoma. A healthy 31-year-old man, who had progressive vision loss in the right eye during 1 month, was found to have a yellow-white juxtapapillary choroidal mass. Fluorescein angiography demonstrated a choroidal neovascular membrane over the lesion. There was focal persistent hypofluorescence in the late phase of fluorescein angiography. The thickness of the lesion increased from 3.0 mm to 7.1 mm during 1 month. Subretinal and vitreous hemorrhage developed. The patient was suspected to have a choroidal granuloma and choroidal neovascular membrane, and was treated with oral steroids. Ten months later, the vitreous blood cleared completely with an attached retina. Control of inflammation may have a role in the treatment of idiopathic choroidal granulomas and some choroidal neovascular membranes secondary to ocular inflammation.     

Krypton laser suture lysis

PURPOSE: To analyze indocyanine green angiography (ICGA) features in two cases of sympathetic ophthalmia using a standard angiography protocol for posterior uveitis. METHODS: Report on two patients who suffered from penetrating ocular injuries 45 and 8 years before sympathetic ophthalmia was diagnosed and confirmed by histopathological examination of the enucleated eye. In addition to routine examination and fluorescein angiography, initial and follow-up ICGAs were performed. RESULTS: The first patient, with a phthisic right eye following s shotgun injury, consulted 6 months after cataract extraction in his good left eye for progressive visual loss due to a neovascular membrane in a moderately inflamed eye. The second patient consulted 8 years after a perforating injury of his right eye by a metallic foreign body because of recent visual loss and inflammation in his good left eye. ICGA of both patients showed numerous hypofluorescent dark dots visible at the intermediate phase, some becoming isofluorescent at the late phase and resolving after long-term corticosteroid therapy, others remaining hypofluorescent until the late phase. CONCLUSION: The two patterns of hypofluorescent areas, either persisting throughout angiography or fading in the late phase, were interpreted respectively as cicatricial and active lesions. ICGA gave determining additional information on choroidal involvement and on subsequent evolution of lesions.     

Clinicopathologic findings in recurrent choroidal melanoma after transpupillary thermotherapy

OBJECTIVE: This study aimed to report the clinicopathologic findings of recurrent choroidal melanoma after transpupillary thermotherapy (TTT). DESIGN: Two case reports. METHODS: The clinical histories and ophthalmologic findings of two patients with recurrent choroidal melanomas who did not respond to TTT were reviewed. Both patients had their eyes with the melanoma enucleated and processed routinely for light and electron microscopic examination. MAIN OUTCOME MEASURES: The eyes were examined for histopathologic and ultrastructural findings. RESULTS: Histopathologic examination showed choroidal melanomas with extensive tumor necrosis and hemorrhage. In areas, tumor cells appeared histologically intact and presumably viable, with ultrastructural evidence of melanogenesis. The eye from one patient was treated only with TTT and showed hemorrhagic necrosis with cytolysis and no changes to tissues surrounding the melanoma. The eye from the other patient, treated with TTT and a radioactive isotope of iodine (I125) plaque, exhibited areas of intact tumor, tumor necrosis, fibrosis, and radiation retinopathy. CONCLUSIONS: These two cases among a total treated series of 14 patients represent examples of uveal melanoma regrowth after TTT. Opaque media precluded adequate treatment in the first case that showed some TTT effect. The second case showed a combination of TTT and I125 effect and failed because of the aggressive nature of tumor.     

Nutrition and osteoporosis

PURPOSE: To establish an animal model of extrascleral extension of choroidal melanoma. METHODS: Pigmented choroidal tumors were established in nine New Zealand albino rabbit eyes using B16F10 melanoma cell line. The sclerotomy site was not closed in the subgroup of six rabbits where extrascleral extension was desired. For the control group, the sclerotomy site was sutured with 8-0 nylon. Animals were treated with daily injections of cyclosporine and followed by serial fundus examinations, color Doppler imaging, and fundus photography. All tumor-bearing eyes were enucleated at the end of the follow-up period and examined for extrascleral extension. RESULTS: Extrascleral extension of choroidal melanoma occurred in all six animals with open sclerotomy sites. No extrascleral extension was observed in the control group. Color Doppler imaging identified extrascleral extension which was confirmed on gross histology. CONCLUSIONS: Our animal model of extrascleral extension of choroidal melanoma requires minimal surgery to establish, and is reproducible and easy to follow with standard diagnostic equipment.     

Delivery, distribution, and neuronal uptake of exogenous mannose-terminal glucocerebrosidase in the intact rat brain

OBJECTIVE: To show the utility of ultrasound biomicroscopy (UBM) in imaging small ocular foreign bodies of the anterior segment. DESIGN: Retrospective case series. PARTICIPANTS: Twelve eyes of 12 consecutive patients evaluated in the emergency department or referred to specialty services at 1 institution between August 1994 and November 1997 were examined. INTERVENTION: Ocular ultrasound biomicroscopy was performed. MAIN OUTCOME MEASURES: Detection and localization of an ocular foreign body were measured. RESULTS: An intraocular or superficial foreign body was detected by UBM in 9 (75%) of 12 eyes. The foreign body was classified as corneal in two eyes, subconjunctival in two, intrascleral in three, and intraocular in two eyes. The foreign body was not visible by ophthalmic physical examination in seven of the nine eyes with a confirmed ocular foreign body. In the remaining two eyes, UBM was used to determine the depth of a visible foreign body. In three of the eyes with a confirmed foreign body, computed tomography and/or contact B-scan ultrasonography was obtained and failed to show a foreign body. Six of the foreign bodies were nonmetallic. CONCLUSIONS: Clinical detection of ocular foreign bodies after trauma can be hindered by small size, haziness of the optical media, poor patient cooperation, or hidden location. Ultrasound biomicroscopy is a valuable adjunct in the evaluation of suspected ocular foreign bodies, especially in cases involving small, nonmetallic objects.     

Choroidal tuberculosis diagnosed by polymerase chain reaction. A clinicopathologic case report

PURPOSE: To show the use of the polymerase chain reaction (PCR) in a granulomatous choroidal lesion to support a diagnosis of tuberculosis. DESIGN: Observational case report. TESTING: Nucleic acid target amplification of a choroidal specimen using PCR for detection of Mycobacterium tuberculosis was tested. MAIN OUTCOME MEASURES: Positive nucleic acid target amplification for M. tuberculosis in the ocular sample was measured. RESULTS: PCR was positive for M. tuberculosis with appropriate negative controls. CONCLUSIONS: PCR was thought to be a useful supportive technique in the diagnosis of choroidal tuberculosis.     

Recombinant GM2-activator protein stimulates in vivo degradation of GA2 in GM2 gangliosidosis AB variant fibroblasts but exhibits no detectable binding of GA2 in an in vitro assay

OBJECTIVE: To examine choroidopathy in patients with Beh?et disease. DESIGN: Prospective clinical study. PARTICIPANTS: Thirty-three patients (63 eyes) with Beh?et disease. INTERVENTION: Patients underwent simultaneous indocyanine green (ICG) and fluorescein angiography with a double detector of scanning laser ophthalmoscopy. MAIN OUTCOME MEASURES: Angiographic findings recorded on videotapes were evaluated. The relation of angiographic findings with systemic activity and aqueous inflammation was also analyzed. RESULTS: Fluorescein angiography showed leakage in varying degrees from retinal vessels in 30 patients (53 eyes, 84%). The ICG angiographic findings were choroidal vascular wall staining in 16 eyes (25%), hyperfluorescent spots in 42 eyes (66%) and hypofluorescent plaques in 22 eyes (35%), both of which were not evident with fluorescein, leakage from choroidal vessels in 3 eyes (5%), and irregular filling of choriocapillaris in 11 eyes (17%). These findings did not have a statistically significant correlation with the presence or absence of aqueous inflammation or oral aphthous ulcerations. CONCLUSIONS: The patients with Beh?et disease showed choroidal abnormalities, which could be revealed only by ICG angiography, but not with funduscopy or fluorescein angiography. Simultaneous ICG and fluorescein angiography would be useful for examining choroidal lesions in Beh?et disease.     

Intraocular invasion by papillary squamous cell carcinoma of the conjunctiva

Two patients with incompletely excised invasive papillary squamous cell carcinoma of the corneoscleral limbal conjunctiva had subtle clinical signs suggesting incomplete transmural extension or localized intraocular tumor invasion. We attempted a wide en bloc resection procedure in each case. Histopathologic examination disclosed that the surgical margins were involved with tumor cells and the eyes were subsequently enucleated. The enucleated eyes disclosed more extensive microscopic intraocular involvement than had been anticipated.     

Long-term follow-up after endoscopic sphincterotomy for bile duct stones in patients younger than 60 years of age

PURPOSE: To study the clinical histories and courses of six patients with choroidal neovascularization secondary to endogenous Candida albicans chorioretinitis. METHODS: The medical records, fundus photographs, and fluorescein angiograms of six patients who developed C. albicans chorioretinitis secondary to candidemia and who subsequently developed choroidal neovascularization in one or both eyes were reviewed. RESULTS: The six patients ranged in age from 18 to 79 years. Four were women and two men; all but one showed evidence of bilateral chorioretinal scarring secondary to C. albicans chorioretinitis. All patients had been treated successfully with systemic antifungal therapy (amphotericin B). Two weeks to two years after the chorioretinitis, choroidal neovascularization developed in one eye (four cases) or both eyes (two cases). The neovascularization on initial examination was subfoveal in four eyes, extrafoveal in three eyes, and juxtafoveal in one eye. Laser photocoagulation was used in four of the eight involved eyes. In these cases, the active choroidal neovascularization was brought under control. In one eye, the patient had submacular surgery for excision of the choroidal neovascular membrane. Final visual acuities ranged from 20/20 to 20/200 in treated eyes and from 20/50 to 20/400 in untreated eyes. CONCLUSION: Choroidal neovascularization is a potential cause of late visual loss in patients who have had C. albicans sepsis and endogenous C. albicans chorioretinitis. Eyes that have chorioretinal scarring from C. albicans chorioretinitis should be watched for the development of choroidal neovascularization. Laser photocoagulation or perhaps surgical excision of the neovascular complex may be of benefit in selected cases.     

Physical and linkage mapping of human chromosome 17 loci to dog chromosomes 9 and 5

We performed fluorescein and indocyanine green (ICG) angiographies in 56 patients with central serous chorioretinopathy, and studied the choroidal lesions. In the early phase, choroidal filling with ICG was delayed in 77% in the area including focal leakage. Hypofluorescent findings around the site of focal leakage persisted through the phase in 23%, and we think this finding was caused by filling defect of the choriocapillaris. In the late phase, choroidal tissue staining by ICG was present in 82% in the area including focal leakage. Multiple areas of choroidal staining were also present in unaffected areas in 43% and in 62% of fellow eyes. Choroidal tissue staining by ICG was revealed in 48% in the area of choroidal filling delay, and this finding persisted after focal leakage had disappeared following photocoagulation. We think this finding was caused by choroidal vascular hyperpermeability. These findings suggest that choroidal circulatory disturbance and choroidal vascular hyperpermeability play a causative role in damage to the retinal pigment epithelium in central serous chorioretinopathy.     

Cerebral MRI of very low birth weight children at 6 years of age compared with the findings at 1 year

The objective was to describe a new surgical technique to manage a posteriorly dislocated crystalline lens. Four patients with posteriorly dislocated lenses were studied. Two patients had dislocated lenses secondary to trauma, 1 had undergone retinal detachment surgery, and 1 had an idiopathic lens dislocation. Pars plana vitrectomy was carried out on all 4 eyes, followed by an injection of perfluoro-n-octane to float the lens off the retina. The lens was phacoemulsified through a limbal incision, and an intraocular lens was positioned in the ciliary sulcus with suture fixation. Perfluoro-n-octane was replaced by a balanced salt solution. Postoperative visual acuity ranged from 1.0-1.5. Transient choroidal detachment and hypotony were observed in 3 eyes in the early postoperative period. Postoperative ocular hypertension was noted in 2 eyes and was well-controlled with topical antiglaucoma agent. These results indicate that limbal lensectomy of a posteriorly dislocated lens using perfluorocarbon liquids is a beneficial and relatively safe method.     

Application of the dispersion model for description of the outflow dilution profiles of noneliminated reference indicators in rat liver perfusion studies

Recent investigations have raised the possibility that ocular diurnal rhythms might be involved in the regulation of eye growth. Specifically, the chick eye elongates with a daily rhythm, said to be absent in form-deprived eyes. The present study asks: (1) Which components of the eye have daily rhythms-only the overall eye size, or also choroidal thickness or anterior chamber depth? (2) Does the phase or amplitude of these rhythms differ in eyes growing either faster than normal (form-deprived eyes) or slower than normal (eyes recovering from form-deprivation myopia)? Using high-frequency A-scan ultrasonography that allowed fine (8-20 micron) resolution of anterior chamber depth, vitreous chamber depth, choroidal thickness and axial length, we measured normal eyes, form-deprived eyes and eyes recovering from form-deprivation myopia at 6 hour intervals for 5 days and 4 nights. All eyes showed daily rhythms in axial elongation and choroidal thickness. In both normal and form-deprived eyes, the axial length was greatest in the afternoon when the choroid was thinnest, and hence, these rhythms were approximately in anti-phase to one another; in addition, there is some evidence that the axial length rhythm in form-deprived eyes is phase-advanced relative to that of their fellow control eyes. The amplitude of the rhythm in choroidal thickness in form-deprived eyes was significantly larger than in normal eyes. In recovering eyes in which elongation is slowed, the rhythm in axial length was significantly phase-delayed relative to normal eyes (peak at 8 pm) and the rhythm in choroidal thickness was phase-advanced (peak at 8 pm); thus in these eyes, the two rhythms are in phase. In these eyes, the choroids were thickening by approximately 100 micron/day. In all three groups, the rhythm in anterior chamber depth appears to differ in phase from the rhythm in axial length (and hence from the rhythm at the posterior wall of the eye). We propose that the phase relationship between these choroidal and eye length rhythms influence the rate of growth of the eye, and conclude that diurnal ocular rhythms may be important in eye growth regulation.     

Photocoagulation of well-defined choroidal neovascularization in age-related macular degeneration: clinicopathologic correlation

PURPOSE: To present the clinicopathologic features of the eyes of a patient with age-related macular degeneration (ARMD): the right eye was treated for well-defined extrafoveal choroidal neovascularization (CNV), and the left eye had an untreated disciform scar. METHODS: The patient was studied ophthalmoscopically and by fluorescein angiography at the time of presentation and on follow-up examinations up to 54 days after laser treatment, when he died. The posterior portions of both eyes (obtained postmortem), including the macula and optic nerve head, were sectioned serially for light microscopy. Tissue sections from both eyes were removed from glass slides and studied by transmission electron microscopy. RESULTS: Histopathologic study of the right eye disclosed a thin layer of basal laminar deposit throughout the posterior pole. Two defects in Bruch's membrane without CNV were present within the area of laser photocoagulation located superior to the fovea. No CNV was present in the scar. Eleven areas of early CNV were present in the posterior pole. Histopathologic study of the left eye showed a prominent basal laminar deposit throughout the posterior pole. A 2.6 x 2.7 mm disciform scar was present that was located mostly in the subretinal space. Four sources of CNV were present. CONCLUSIONS: The clinicopathologic features of a treated eye with well-defined extrafoveal CNV, and the fellow eye with a disciform scar, both associated with ARMD, are presented. Although laser treatment obliterated a choroidal neovascular membrane, 11 additional areas of early, subclinical CNV were present.     

Histology of posterior scleral foramen in normal eyes: its possible role in optic nerve damage in chronic open angle glaucoma

We examined the histologic features of the posterior scleral foramen in 27 enucleated eyes (16 during autopsy and 11 with choroidal malignant melanoma). The histologic findings of the posterior scleral foramen were similar to those in previous reports. The shape of the scleral foramen was either cylindrical or truncated, the latter occurring when the inner margin of the sclera projected with a crest-like edge pressing into the optic nerve. This configuration was encountered more frequently in the upper and lower temporal aspects of the scleral foramen in 10 eyes, while the nasal rim was free of such projection in all the eyes. We hypothesize that the effect of prolonged high intraocular pressure exerted on the axonal tissue against these crest-like edges of the non-distensible scleral foramen might be the major factor in the etiology of early arcuate nerve fiber bundle defects in primary open-angle glaucoma.     

Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins

OBJECTIVE: The study aimed to assess the frequency, indications, and outcome of additional ocular procedures after initial treatment of vitrectomy (VIT) or tap-biopsy (TAP) for patients with endophthalmitis after cataract extraction. DESIGN: The study design was an analysis of observational data collected as part of a multicenter, randomized clinical trial. PARTICIPANTS: Of the 420 patients enrolled in the Endophthalmitis Vitrectomy Study, the 148 who had additional procedures were compared with the 272 who did not. MAIN OUTCOME MEASURES: The types, indications, and number of additional ocular procedures were assessed. A masked examiner measured visual acuity 9 to 12 months after study entry. RESULTS: Within 1 week of study entry, 8% of VIT eyes and 13% of TAP eyes underwent additional procedures, 14% for complications of the initial procedure and 86% for worsening ocular inflammation or infection. Cultures were obtained in 33 of the 38 eyes operated on for worsening inflammation or infection and were positive in 42%. Cultures obtained from the early additional procedures were positive more frequently in eyes with an initial TAP (71%) than in eyes with an initial VIT (13%). Both virulence of initial microbiologic organism isolated and poor presenting vision were risk factors for requirement of reoperation. In all cases in which a single organism was cultured at the initial procedure, when the reculture was positive, it was the same organism. Late additional procedures (after 7 days) were required in 27% of patients. Visual outcome was much worse for eyes that had an additional procedure compared to eyes that did not, and this was especially the case for eyes that had an early additional procedure. Only 15% of eyes that had an early additional procedure achieved 20/40 visual acuity as compared to 57% of eyes that did not. CONCLUSION: Need for an additional procedure was a marker of more severe disease, and patients who underwent additional procedures achieved poorer visual acuity at final follow-up.     

Irregular retinal and RPE damage after pressure-induced ischemia in the rabbit

PURPOSE: Pressure-induced ocular ischemia is a frequent model for the investigation of the mechanisms and therapy of retinal ischemic damage. It is important to know whether the tissue damage in such experiments is uniform or irregular. METHODS: We reviewed histologic features of Dutch rabbit eyes after 60-80 min of pressure-induced ischemia. The eyes were enucleated 4 hr, 1 day, or 1 wk after circulation was restored, at which times the electroretinogram b-wave was moderately reduced. RESULTS: Light microscopy showed an irregular distribution of damage involving all retinal layers and retinal pigment epithelium. Some regions of damage (or preservation) were several millimeters wide; others were as small as a few cell widths. Correlation with electroretinogram reduction in individual eyes was difficult. CONCLUSIONS: These results show that pressure-induced ischemic damage in the rabbit, sufficient to reduce the electroretinogram, has a patchy and irregular effect on retina and retinal pigment epithelium. Erroneous judgments may be made about ischemic damage, or therapeutic intervention, if only small or selected regions of retina are examined histologically.     

The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma

OBJECTIVE: To determine the outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma. METHODS: Prospective analysis of 27 eyes in 22 patients with group V retinoblastoma treated with either 2- or 6-cycle chemoreduction and focal treatment methods (argon laser photocoagulation, transpupillary thermotherapy, cryotherapy, and plaque radiotherapy). The need for external beam irradiation and the eventual globe salvage rate were assessed. Median follow-up was 28 months. RESULTS: There were 16 eyes in the 2-cycle chemoreduction treatment group and 11 eyes in the 6-cycle chemoreduction treatment group. No significant difference was noted between the 2 groups with respect to baseline patient and eye findings. After chemoreduction treatment, external beam irradiation was necessary in 12 (75%) of 16 eyes in the 2-cycle chemoreduction treatment group and in 4 (36%) of 11 eyes in the 6-cycle chemoreduction treatment group. There was no statistical difference between the 2- and 6-cycle chemoreduction treatment groups with respect to necessity for external beam irradiation (logistic regression analysis). All 4 eyes in the 2-cycle chemoreduction treatment group and 3 of 12 eyes in the 2-cycle chemoreduction treatment and irradiation group were eventually enucleated, the globe salvage rates being 0% and 75%, respectively. Two of 7 eyes in the 6-cycle chemoreduction treatment group and 1 of 4 eyes in the 6-cycle chemoreduction treatment and irradiation group were enucleated, the globe salvage rates being 71% and 75%, respectively. Except for the 2-cycle chemoreduction treatment group, in which the globe salvage rate was significantly lower (P = .03), there was no difference among the other 3 groups (2-cycle chemoreduction treatment and irradiation, 6-cycle chemoreduction treatment, and 6-cycle chemoreduction treatment and irradiation) with respect to globe salvage (logistic regression analysis). CONCLUSIONS: Local tumor control of group V retinoblastoma is possible with 6-cycle chemoreduction and focal therapy when external beam irradiation is not used. A larger sample size is necessary to determine how often external beam irradiation can be avoided.     

Successful bone marrow transplantation in a Chinese boy with Wiskott-Aldrich syndrome

BACKGROUND: Choroidal ruptures occurring as a result of blunt ocular injury are uncommon. A 72-year-old woman sustained blunt trauma to the left eye in 1965. In 1986, she was seen at the Wilmer Institute, and posterior choroidal rupture was documented and fluorescein angiography was performed. Absence of fluorescence was seen in the area of the rupture, and the inferotemporal artery and vein dipped into the area and emerged on the other side of the rupture. METHODS: The eyes were obtained postmortem, and histologic examination was performed. RESULTS: Examination of the left eye revealed a horizontal linear white scar inferior to the optic nerve and macula. Stepped-serial sections through the rupture revealed a 0.7-mm wide defect in Bruch's membrane and retina where fibrous tissue containing melanocytes extended into the vitreous cavity for a short distance. CONCLUSION: The clinicopathologic features of an indirect horizontal choroidal rupture is reported.