Significant head cooling can be achieved while maintaining normothermia in the newborn piglet.

BACKGROUND: Hypothermia has been shown to be neuroprotective in animal models of hypoxia-ischaemia. It is currently being evaluated as a potentially therapeutic option in the management of neonatal hypoxic-ischaemic encephalopathy. However, significant hypothermia has adverse systemic effects. It has also recently been found that the stress of being cold can abolish the neuroprotective effects of hypothermia. It is hypothesised that selective head cooling (SHC) while maintaining normal core temperature would enable local hypothermic neuroprotection while limiting the stress and side effects of hypothermia. OBJECTIVE: To determine whether it is possible to induce moderate cerebral hypothermia in the deep brain of the piglet while maintaining the body at normothermia (39 degrees C). METHODS: Six piglets (<48 hours old) were anaesthetised, and temperature probes inserted into the brain. Temperature was measured at different depths from the brain surface (21 mm (T(deep brain)) to 7 mm (T(superficial brain))). After a 45 minute global hypoxic-ischaemic insult, each piglet was head cooled for seven hours using a cap circulated with cold water (median 8.9 degrees C (interquartile range 7.5-14)) wrapped around the head. Radiant overhead heating was used to warm the body during cooling. RESULTS: During SHC it was possible to cool the brain while maintaining a normal core temperature. The mean (SD) T(deep brain) during the seven hour cooling period was 31.1 (4.9) degrees C while T(rectal) remained stable at 38.8 (0.4) degrees C. The mean T(rectal)-T(deep brain) difference throughout the cooling period was 9.8 (6.1) degrees C. The mean T(skin) required was 40.8 (1.1) degrees C. There was no evidence of skin damage secondary to these skin temperatures. During cooling only one piglet shivered. CONCLUSIONS: It is possible to maintain systemic normothermia in piglets while significantly cooling the deeper structures of the brain. This method of cooling may further limit the side effects associated with systemic hypothermia and be feasible for premature infants.

Cataracts in patients heterozygous for galactokinase deficiency.

The role of heterozygous galactokinase deficiency in the development of presenile cataracts is presently undetermined. Erythrocyte galactokinase activity was measured from 95 normal Caucasian subjects and from 39 Caucasian patients who had developed idiopathic bilateral cataracts between ages 20 and 55. The diagnosis of heterozygous galactokinase deficiency was based on the following criteria: galactokinase activity more than 2.0 SD below the control population mean; when available, familial evidence for heterozygous galactokinase activity was used as additional evidence. Three of 39 patients (1/13) with cataracts were found to be carriers of the galactokinase deficiency allele (P less than 0.001). Two heterozygotes had high dietary galactose intake suggesting a possible relationship between a high galactose diet and cataract formation. Dietary information was unavailable for the third heterozygote. We conclude that there is a high prevalence of heterozygous galactokinase deficiency existing in patients less than 55 yr of age with cataracts, and recommend that adults at risk restrict their consumption of dairy products.

Prenatal diagnosis of Fraser syndrome at 18.5 weeks gestation, with autopsy findings at 19 weeks.

Sonography permitted the diagnosis of Fraser syndrome (cryptophthalmos-syndactyly syndrome) at 18.5 weeks of gestation in a fetus whose parents had had a previous affected child. The karyotype of that child was 46,XX,inv(9)(p11q21); the karyotype of the phenotypically normal father and of the fetus was 46,XY,inv(9)(p11q21). Findings on sonography included oligohydramnios with nonvisualization of kidneys, hypertelorism and microphthalmia, and markedly enlarged lungs. On autopsy at 19 weeks, findings included renal agenesis, cryptophthalmos with multiple abnormalities of the eyes and ocular adnexa, laryngeal atresia, pulmonary hyperplasia with accelerated maturation, absence of the Eustachian tube with connective tissue occupying the tympanic cavity and bone occluding the external acoustic meatus, and soft-tissue webbing between the digits. This is the second reported instance of prenatal diagnosis of Fraser syndrome in the second trimester. The histopathologic findings in Fraser syndrome at this gestational age, in particular the eye and ear, have not been described previously.

Pseudo-Schnabel's cavernous degeneration of the optic nerve secondary to intraocular silicone oil.

A 29-year-old man sustained severe trauma to his left eye requiring corneoscleral wound repair and retinal detachment repair. Because of a persistent retinal detachment, he underwent vitrectomy and silicone oil implantation into the vitreous cavity. Over the ensuing 2 years 4 months, the eye gradually became glaucomatous, blind, and painful, requiring enucleation. Histopathologic examination revealed that coalescent globules of silicone oil had infiltrated the entire length of the attached atrophic optic nerve. Superficially reminiscent of the changes seen in Schnabel's cavernous optic atrophy, this observation provides evidence for the theory of Zimmerman et al concerning the pathogenesis of cavernous degeneration of the optic nerve in glaucomatous eyes.

Malignant melanoma arising from unusual conjunctival blue nevus.

Cellular blue nevus is an uncommon pigmented tumor in the conjunctiva, where it generally appears as a deep, circumscribed, pigmented conjunctival mass. We report a case of conjunctival blue nevus that clinically resembled primary acquired melanosis and gave rise to conjunctival melanoma. A 41-year-old man developed a diffuse pigmented mass in the inferior fornix of his left eye. Over a 20-year period, he noted slight progression of the pigment. Foci of epibulbar pigmentation were also present. The lesion resembled primary acquired melanosis. Excisional biopsy and adjuvant cryotherapy were performed. Histopathologic examination disclosed an intense infiltrate of heavily pigmented dendritic melanocytes with aggregates of less pigmented plump cells in the substantia propria. The conjunctival epithelium was normal. Malignant cellular features consistent with melanoma were observed in some foci. Cellular blue nevus of the conjunctiva can simulate primary acquired melanosis and can give rise to malignant melanoma. Arch Ophthalmol. 2000;118:1581-1584

Choroidal metastasis as the initial manifestation of a pigmented neuroendocrine tumor.

We report the case of a 77-year-old woman in whom choroidal metastasis was the initial manifestation of a primary neoplasm presumed to be a pigmented pulmonary carcinoid tumor. The tumor initially was misdiagnosed cytologically and pathologically as a choroidal melanoma because it contained intrinsic melanin pigment. Positive immunoreactivity for cytokeratin, synaptophysin, chromogranin, and calcitonin and the presence of dense-core neurosecretory vesicles disclosed by electron microscopy established that the metastasis was a neuroendocrine tumor. Findings from systemic evaluation suggested that the primary tumor was located in the lung. The patient subsequently developed an intradural paraspinal metastasis, which also contained melanin pigment. The latter observation confirmed that the melanin in the uveal metastasis was intrinsic and did not represent secondary phagocytosis by tumor cells. Metastases from pigmented tumors of nonmelanocytic derivation are exceedingly rare but present a major diagnostic challenge to ocular pathologists and cytopathologists if the diagnosis is not suspected. Confirmatory immunohistochemical analysis should be obtained when a pigmented choroidal tumor thought to be a melanoma has atypical features. Arch Ophthalmol. 2000;118:841-845

Adenoma of the ciliary body pigment epithelium: the 1998 Albert Ruedemann, Sr, memorial lecture, Part 1.

BACKGROUND: Adenoma of the pigment epithelium of the ciliary body (CPE) is a rare neoplasm. Most reported cases have been misdiagnosed as ciliary body melanoma. OBJECTIVES: To evaluate clinical features, management, pathological features, and prognosis of adenoma of the CPE and to determine clinical features that may differentiate it from ciliary body melanoma. PATIENTS AND METHODS: A retrospective review was performed of medical charts, photographs, and pathological features of patients with adenoma of the CPE who were treated by the authors. RESULTS: Of the 8 patients with adenoma of the CPE, 3 were male and 5 were female. Seven were white, and 1 was Asian. The mean age at diagnosis was 51 years (range, 8-73 years). The referring diagnosis was ciliary body melanoma in 7 patients and cyst in 1 patient. The lesions were all solitary and unilateral and ranged from 3 x 3 x 3 to 13 x 13 x 8 mm. Clinically, all tumors were gray to black, had abruptly elevated margins, and were dome shaped. Associated findings included secondary cataract (6 patients) and vitreous hemorrhage (1 patient). Results of ancillary studies such as transillumination, fluorescein angiography, and ultrasonography showed patterns that were helpful in differentiation from ciliary body melanoma. Fine needle aspiration biopsy, performed in 3 patients, was an accurate diagnostic adjunct. Microscopic diagnosis was adenoma of the CPE in 7 cases in which tissue was available. A consistent histopathologic feature was the presence of typical clear vacuoles within the tumor. One tumor invaded the sensory retina. Results of immunohistochemical studies were consistent with a tumor of neuroectodermal origin. CONCLUSIONS: Adenoma of the CPE has characteristic features that may help differentiate it from ciliary body melanoma. In contrast to melanoma, it is generally darker and its margins are more abruptly elevated. Although it is benign cytologically, it can exhibit growth. If the diagnosis is suspected, removal of the tumor by local resection is advisable.

Neoplasms of the retinal pigment epithelium: the 1998 Albert Ruedemann, Sr, memorial lecture, Part 2.

BACKGROUND: Neoplasms of the retinal pigment epithelium (RPE) are rare, and little is known about their clinical variations, clinical course, and prognosis. Although most are benign, they can simulate choroidal melanoma. OBJECTIVES: To evaluate the clinical characteristics, management, pathological features, and prognosis of acquired neoplasms of the RPE (adenoma and adenocarcinoma) and to define clinical features that help differentiate them from uveal melanoma. PATIENTS AND METHODS: The medical records of patients with acquired tumor of the RPE were reviewed retrospectively, and the clinical features, management, and histopathologic findings were studied. RESULTS: Of 13 affected patients, 10 were women and 3 were men. Ten were white and 3 were African American. The mean age at diagnosis was 53 years (range, 28-79 years). All patients were referred with the diagnosis of suspected choroidal melanoma. All tumors were solitary, unilateral, and ranged from a small, asymptomatic lesion measuring 2 x 2 x 1 mm to a massive neoplasm that measured 17 x 17 x 17 mm. There was no predilection for retinal location or laterality. The tumors were dark brown to black in 11 patients and only minimally pigmented in 2. Prominent retinal feeder vessels were visualized in 8 patients, 5 of whom had an exudative retinal detachment. Two patients had recurrent vitreous hemorrhage. Transillumination generally revealed blockage of light by the tumor. Fluorescein angiography showed early hypofluorescence and late minimal hyperfluorescence of the tumor, without visibility of choroidal vessels. Ultrasonography typically demonstrated the tumor to be abruptly elevated and to have medium to high internal reflectivity and acoustic solidity. Results of diagnostic fine needle aspiration biopsy, performed on 4 patients, disclosed cells compatible with a pigment epithelial origin. Treatment ultimately included observation in 4 patients, enucleation in 3, local tumor resection in 3, irradiation in 2, and laser therapy in 1. Microscopic verification of the diagnosis was available in 3 eyes after fine needle aspiration biopsy, 3 eyes after local resection, 3 eyes after enucleation, and 1 eye post mortem. The microscopic diagnosis was adenoma in 8 patients and adenocarcinoma in 2. Microscopically, the lesions were composed of a neoplastic proliferation of RPE cells. Tumors arising from the anterior portion of the RPE had a vacuolated pattern, and those in the posterior portion of the RPE had a glandular or tubular configuration. CONCLUSIONS: Neoplasms of the RPE show considerable clinical variation. In contrast to melanoma, they generally are darker, more abruptly elevated, and more likely to have retinal feeder vessels and exudative retinal detachment; show early hypofluorescence and mild late hyperfluorescence on angiographic findings; and have high internal reflectivity on ultrasonographic findings. Although most acquired tumors of the RPE are benign cytologically, they can exhibit aggressive clinical behavior.

Proliferative endotheliopathy with iris abnormalities. The iridocorneal endothelial syndrome.

Sixteen cases of essential iris atrophy and two of iris nevus (Cogan-Reese) syndrome were reviewed retrospectively by light and electron microscopy. Varying degrees of corneal endothelial proliferation onto the trabecular meshwork and anterior iris were seen in all cases. The demonstration of an endothelial-abnormal basement membrane complex on the anterior iridic surface, deep to synechias in over half the cases, indicates that endothelialization may be primary, since it precedes the formation of anterior synechias. Pathologic and clinical evidence suggests that the iris nevus syndrome, Chandler's syndrome, and essential iris atrophy represent a continuum of clinical manifestations of a single disease process involving proliferation of the corneal endothelial and characteristic iris abnormalities; the latter may be secondary to variations in the pattern, rate, and extent of endothelial proliferation. We suggest the term "proliferative endotheliopathy" to emphasize the common pathogenetic role of corneal endothelial proliferation in all three entities (iris nevus syndrome, Chandler's syndrome, and essential iris atrophy). A more succinct alternate term is "the iridocorneal endothelial (ICE) syndrome."

The basement membrane exfoliation syndrome.

Previous observations suggest that "pseudoexfoliation of the lens capsule" may be a disease in which cells produce abnormal basement membrane material. Electron microscopic studies indicate that exfoliative material can be produced by cells throughout the anterior segment of the eye. This report describes abundant exfoliative material on the ciliary and iridic epithelia but not on the surface of the lens whose epithelial cells were completely necrotic. Exfoliative material also was observed in the anterior iridic stroma close to a newly formed abnormal endothelial basement membrane, suggesting that exfoliative material may be produced locally within the iris. Furthermore, typical exfoliative material, best considered a filamentous, banded basement membrane with 500-A periodicity, in the wall of a short posterior ciliary artery in the orbit indicates that the exfoliative process is not solely limited to ocular tissues. The term "basement membrane exfoliation syndrome" is proposed for this entity.

Early-onset scleral necrosis after iodine I 125 plaque radiotherapy for ciliochoroidal melanoma.

A 62-year-old man with a large ciliochoroidal melanoma developed early-onset scleral necrosis with tumor extrusion within 1 month of epibulbar iodine I 125 plaque radiotherapy. The eye was enucleated. Pathologic study revealed nonmicrobial scleral necrosis with extrusion of histologically intact and necrotic uveal melanoma cells. The patient has been followed up for 15 months without clinical recurrence. We discuss possible mechanisms to explain the early development of scleral necrosis after plaque therapy in this patient.

Adenoma of nonpigmented ciliary epithelium with smooth muscle differentiation.

A 35-year-old man underwent successful iridocyclectomy for a ciliary body mass that was subluxating the lens and causing a secondary cataract. Histopathologically the mass proved to be a spindle cell tumor, but leiomyoma and melanoma were initially considered to be diagnostic possibilities. However, further studies and immunohistochemical studies revealed that the tumor probably arose from the nonpigmented ciliary epithelium. The spindle cells represented smooth muscle differentiation within the mass. The final diagnosis was adenoma of the nonpigmented ciliary epithelium with smooth muscle differentiation.

Parry-Romberg syndrome associated with intracranial vascular malformations.

We describe a 23-year-old woman with iridocyclitis, enophthalmos, facial hemiatrophy, and transient numbness of her contralateral upper and lower extremities. The patient was found to have white matter densities in the right hemisphere in magnetic resonance T2-weighted images and vascular malformations involving right vertebral, right carotid, and right anterior cerebral arteries. Histopathologic evaluation of a biopsy specimen of anterior orbital fat and lacrimal gland revealed fibrosis and chronic inflammation. These findings were consistent with the diagnosis of progressive facial hemiatrophy (Parry-Romberg syndrome) in association with iridocyclitis and intracranial vascular malformations.

Presumed adenocarcinoma of the retinal pigment epithelium in a blind eye with a staphyloma.

The retinal pigment epithelium (RPE) can undergo reactive hyperplasia and metaplasia following a variety of ocular insults. However, true neoplasms of the RPE are rare. We report a case of a papillary adenocarcinoma of the RPE arising in the blind staphylomatous right eye of a 79-year-old woman with a long history of bilateral posterior staphylomas who was seen with increasing pain and exophthalmos of the right eye. Findings from ultrasonography and computed tomography demonstrated linear calcification consistent with osseous metaplasia of the RPE. Progression of the exophthalmos and worsening exposure keratitis led to enucleation of the eye. Gross pathology showed a 79-mm-long globe. Histopathologic findings revealed a largely amelanotic papillary adenocarcinoma arising from the RPE. Positive immunoreactivity for cytokeratin supported the epithelial origin of the tumor. Adenocarcinoma of the RPE is rare but may develop in a blind eye.

Choroidal melanoma in a 14-year-old patient with ocular melanocytosis.

A 14-year-old male adolescent with ocular melanocytosis and secondary glaucoma in the left eye had a 2-year history of a progressively enlarging fundus lesion. Ocular examination revealed diffuse hyperpigmentation of the episclera and a smooth velvety thickening and hyperpigmentation of the left iris. Ophthalmoscopy disclosed diffuse choroidal pigmentation and a pigmented mass that occupied the macular area and surrounded the optic nerve. Ultrasonography showed an acoustically hollow lesion with scleral bowing and choroidal excavation. Based on clinical and ultrasonographic findings, the diagnosis was choroidal melanoma in a young patient with ocular melanocytosis. The eye was enucleated. Histopathologic examination revealed ocular melanocytosis with diffuse uveal melanocytosis and amelanotic malignant melanoma of the choroid. The choroidal melanoma apparently arose from a preexisting choroidal nevus. Even young patients with ocular melanocytosis should have regular follow-up examinations for early detection of uveal melanoma.

Adenoma of the retinal pigment epithelium simulating a juxtapapillary choroidal neovascular membrane.

We report a case of an adenoma of the retinal pigment epithelium that clinically simulated a juxtapapillary choroidal neovascular membrane in a 60-year-old man. Fluorescein angiography supported the diagnosis of a juxtapapillary choroidal neovascular membrane in his left eye. After 13 years the lesion become slightly pigmented and the optic disc became swollen. The possibility of choroidal melanoma with optic disc invasion was considered, and the eye was enucleated. The lesion proved histopathologically to be an adenoma of the retinal pigment epithelium.

Bilateral Candida parapsilosis endophthalmitis.

We describe a patient with bilateral, delayed endophthalmitis who underwent bilateral pars plana vitrectomy, total capsulectomy, intraocular lens exchange, intravitreal injection of amphotericin B, and oral fluconazole therapy. The long-term inflammation resolved, and vitreous cultures from both eyes yielded Candida parapsilosis. Histopathologic examination revealed sequestered yeast forms in the capsular bags.

Malignant melanoma of the optic nerve.

A 67-year-old man was diagnosed as having a melanocytoma of the optic disc in the left eye. Observation during a 5-year period showed no change in the lesion. At age 72 years, he had abrupt visual loss to no light perception in the affected left eye. Clinical examination disclosed little enlargement of the papillary tumor but ultrasonographic evidence of optic nerve infiltration. Precontrast magnetic resonance imaging studies disclosed a hyperintense infiltrative lesion in the enlarged left optic nerve. Enhancement features of the lesion excluded a hemorrhagic process. The eye was removed with a 22.5-mm segment of optic nerve. Histopathologic examination showed a large, necrotic, mixed-cell malignant melanoma confined to the optic nerve. No choroidal involvement or viable melanocytoma cells were documented. This case stresses that it may be difficult to differentiate a melanocytoma from a primary malignant melanoma of the optic nerve.

Orbital and eyelid involvement with Erdheim-Chester disease. A report of two cases.

Erdheim-Chester disease is an idiopathic condition characterized by infiltration of the heart, lungs, retroperitoneum, bones, and other tissues by a fibrosing xanthogranulomatous process composed of xanthomatous histiocytes and Touton giant cells. This condition is often fatal, with death due to cardiomyopathy, severe lung disease, or chronic renal failure. Ocular findings with this potentially fatal disease are rare. We report the clinical and histopathologic findings in two cases of bilateral xanthelasmas and bilateral orbital infiltrates in association with Erdheim-Chester disease. The first patient was a 38-year-old man with cardiovascular and renal disease and severe retroperitoneal fibrosis. The massive orbital infiltration produced bilateral blindness. The second patient was a 77-year-old man with severe cardiovascular disease and retroperitoneal fibrosis. The diagnosis was confirmed in both patients with retroperitoneal and orbital biopsies. Both patients had the unusual occurrence of bilateral xanthelasmas with bilateral, diffuse orbital masses, eye findings that should alert the clinician to the possibility of this serious systemic disease.

Acute band keratopathy following intracameral Viscoat.

Band keratopathy developed rapidly in two patients following uneventful phacoemulsification and intraocular lens implantation using BSS Plus (balanced salt solution enriched with glutathione, bicarbonate, and glucose) infusion and Viscoat (chondroitin sulfate-sodium hyaluronate), which was left in the anterior chamber at the conclusion of the procedure. Histopathologic evaluation of corneal tissue obtained from one patient at the time of edetic acid chelation revealed histochemical findings consistent with anterior stromal calcification. To investigate a possible relationship between Viscoat and the rapid onset of band keratopathy, Viscoat formulated with varying concentrations of phosphate buffer was injected intracamerally into 42 rabbit eyes. Within 48 hours, clinically obvious corneal opacification developed in nine (47%) of 19 eyes injected with the commercial preparation of Viscoat. Also, similar opacification developed in ten (77%) of 13 eyes that received Viscoat formulated with twice the phosphate concentration of the commercial preparation. Band keratopathy did not develop any of ten eyes that received Viscoat with one fourth the commercial phosphate concentration. In selected opacified corneas, the presence of phosphorus in the subepithelial and posterior corneal stroma was confirmed by histochemical stains and energy-dispersive x-ray analysis.