Ralph C. Eagle

Ocular toxoplasmosis in patients with the acquired immunodeficiency syndrome

In seven of eight cases of presumed ocular toxoplasmosis in patients with AIDS, the diagnosis was supported by a reduction or resolution of intraocular inflammation and healing of necrotic retinal lesions after initiation of antiparasitic drug therapy including one or more of the following medications: pyrimethamine, sulfadiazine, clindamycin, tetracycline, or spiramycin. In two cases the diagnosis was confirmed histologically. The cases differed clinically and histopathologically from those in immunocompetent patients. There was no evidence that disease originated in preexisting retinochoroidal scars. Lesions frequently were bilateral and multifocal. Vitreous inflammatory reaction was a common clinical finding, but histopathologic examination demonstrated scant retinal inflammation in areas of necrosis. Ocular toxoplasmosis in these patients with AIDS probably resulted from newly acquired infection or dissemination of organisms from nonocular sites of disease. Infections became clinically inactive with drug therapy in all treated patients, but reactivation and progression of disease occurred when therapy was stopped in two of three patients. Severe retinal necrosis led to retinal tears or detachment in three cases. Ocular lesions were the first manifestation of Toxoplasma gondii infection in four of five patients with evidence of multisystem infection.

Fine-needle Aspiration Biopsy of Suspected Intraocular Tumors: The 1992 Urwick Lecture

BACKGROUND Fine-needle aspiration biopsy recently has been used as a diagnostic modality for selected intraocular tumors and simulating conditions. However, the value of fine-needle aspiration biopsy for intraocular tumors previously has not been clarified. METHODS Transocular fine-needle aspiration biopsy was performed on selected patients who had intraocular lesions that were suspected clinically to be neoplasms but in which there was diagnostic uncertainty based on noninvasive clinical evaluation. These cases were analyzed to determine accuracy, complications, and limitations of the technique. RESULTS Of 6500 patients referred to the Oncology Service for evaluation of possible intraocular tumor, transocular fine-needle aspiration biopsy was used clinically in 159 cases (2.4%). It proved to be a reliable diagnostic method for intraocular malignancies such as uveal melanoma, uveal metastasis, retinoblastoma, lymphoma, and leukemia. In the 140 cases (88%) in which adequate cytologic material was obtained, the sensitivity rate was 100% and the specificity rate was 98%. In 19 cases where the cytologic material was too scant to render a diagnosis, the sensitivity rate was 84% and the specificity rate was 98%. The problem of insufficient material for cytologic diagnosis has been greatly minimized with the recent use of a 22-gauge needle. The main complication was localized intraocular hemorrhage. Retinal detachment and tumor recurrence have not been observed. CONCLUSIONS Transocular fine-needle aspiration biopsy is a safe and reliable diagnostic method for suspected intraocular tumors and inflammatory conditions in which noninvasive diagnostic modalities have failed to establish the diagnosis and in which cytologic verification of the diagnosis is necessary to institute appropriate treatment. Although the authors have had few complications with fine-needle aspiration biopsy, the technique should be reserved for selected cases where the diagnosis has not been established by less-invasive diagnostic measures.

Cancer metastatic to the orbit: the 2000 Robert M. Curts Lecture.

Purpose To report the demographics and clinical features of a large series of patients with orbital metastasis. Methods Retrospective chart review on 100 consecutive patients and a literature review on orbital metastasis. Results Of 100 patients, the primary tumor site was breast in 53 (53%), prostate gland in 12 (12%), lung in 8 (8%), skin (melanoma) in 6 (6%), kidney in 5 (5%), gastrointestinal tract in 5 (5%), choroid (melanoma) in 2 (2%), parotid gland in 1 (1%), and adrenal gland (neuroblastoma) in 1 (1%). Of patients in whom a detailed history was available, there was no history of cancer at the time of presentation in 19%. In 10%, the primary tumor remained undetected despite systemic evaluation. There were 36 male patients and 64 female patients whose mean age at diagnosis was 62 years (median 60 years, range 5 to 91years). Both the right and left orbits were affected equally, and 4 cases (4%) were bilateral. The most frequent clinical findings were limited ocular motility (54%), proptosis (50%), and palpable mass (43%). The diagnoses were established by history, systemic survey, imaging studies, and biopsy. Treatment included chemotherapy, hormone therapy, irradiation, surgical excision, or observation, depending on clinical circumstances. Among patients with sufficient follow-up, 95% died of metastasis, with overall mean survival of 15 months (median 15 months; range 3 to 96 months) after orbital diagnosis. Conclusions The most common primary cancers that metastasize to the orbit are breast, prostate gland, and lung cancer. In 19%, there is no history of cancer when the patient presents with ophthalmic symptoms and in 10% the primary site remains obscure despite systemic evaluation. The systemic prognosis is generally poor.

Immunohistochemical and ultrastructural studies on the exenterated orbital tissues of a patient with graves' disease

The exenterated orbital contents obtained post mortem from a 47-year-old man who had an eight-month history of treated hyperthyroidism and a two-month history of visual complaints were examined histopathologically, immunohistochemically, and by electron microscopy. All of the extraocular muscles were massively enlarged, due to early diffuse endomysial fibrosis, mucopolysaccharide deposition, and a predominantly perivascular lymphocytic and plasmacytic infiltration. Histochemical stains revealed that the intramuscular mucopolysaccharides were weakly sulfated and polycarboxylated, establishing that they were products of fibroblastic activation rather than derived from mast cells. Subsarcolemmal deposits in the myofibers were shown by electron microscopy to be collections of glycogen rosettes with intermixed lipid deposits. These inclusions were interpreted as secondary phenomena due to abnormal muscle energetics from restrictions in contractility, and not as evidence of a primary degeneration of the extraocular muscle fibers themselves. The sarcomeric organization of the striated muscle cells was undisturbed, and therefore the pathologic changes occurred int he interstitial space of the endomysium. A monoclonal antibody specific for neurofilaments (antibody 4.3 F9) revealed, in comparison with normal controls, a preferential loss of large-type axons of the proximal segment of the orbital portion of the optic nerve as well as in the intracanalicular portion. The axonal loss was associated with a mildly increased number of astrocytes as demonstrated by an antibody against glial fibrillary acidic protein. The meninges of the optic nerve, the orbital fat, and the tendons of the extraocular muscles were uninflamed. The foregoing findings are compatible with a compressive optic neuropathy mediated by the massively swollen extraocular muscles impinging upon the optic nerve at the orbital apex.

Clinicopathologic Review of 142 Cases of Lacrimal Gland Lesions

A review of 142 lacrimal gland biopsies performed during a 25-year period at a major eye hospital showed that 78% of lacrimal gland lesions were of nonepithelial origin and only 22% were primary epithelial neoplasms. The nonepithelial lesions included inflammation (64%) and lymphoid tumors (14%), whereas the epithelial lesions included dacryops (6%), pleomorphic adenoma (12%), and malignant epithelial tumors (4%). These results contradict the much quoted dictum that 50% of lacrimal gland lesions are primary epithelial tumors and 50% are nonepithelial lesions.

Histopathologic Evidence of Fibrovascular Ingrowth Four Weeks After Placement of the Hydroxyapatite Orbital Implant

We studied the histopathologic findings after placement of an orbital hydroxyapatite implant in a patient. The implant was placed after enucleation for a choroidal melanoma and was removed four weeks later because histopathologic examination of the enucleated globe disclosed tumor invasion of the optic nerve that necessitated further orbital tissue removal. Our histopathologic findings confirm that there is significant ingrowth of fibrovascular tissue in these implants, even within weeks of implantation.

Acanthamoeba keratitis: a parasite on the rise.

Purpose: To report a recent significant increase of the number of patients diagnosed with Acanthamoeba keratitis (AK) at Wills Eye Hospital between 2004 and 2005. To determine the risk factors, clinical characteristics, treatments, and outcomes of patients with AK. Methods: Retrospective consecutive case series of 20 eyes with AK. The information included the incidence from 1995 to 2005, initial and final best-corrected visual acuity (BCVA) at 3-month follow-up, risk factors [contact lenses (CL) history, history of swimming with CL, and exposure to well water and/or contaminated water], clinical characteristics, methods of diagnosis, and treatments. Results: A statistically significant increased incidence of AK was seen in 2004 and 2005 compared with cases from 1995 to 2003 (P < 0.01). All patients wore CL; 19 of 20 wore frequent-replacement soft CL and used multipurpose disinfecting solutions. Other risk factors were exposure to well water in 40%, swimming with CL in 25%, and overnight wear in 25%.The diagnosis was made by histopathology in 50%, by microbiology in 15%, and by initial classic clinical signs and response to treatments in 35%. Herpes simplex virus was the misdiagnosis in 70%. Patients who presented with dendritiform keratitis or radial keratoneuritis had a BCVA better than 20/30 in 8 of 9 (89%) and patients with ring ulcers or stromal disease who had a BCVA less than finger counting in 5 of 8 (62.5%). Conclusions: We observed an increased incidence of AK. Patients with proper use of frequent-replacement CL and multipurpose solutions can develop AK. Advanced stromal disease at diagnosis is associated with worse outcome.

Fine-needle aspiration biopsy of suspected intraocular tumors.

Background: Fine-needle aspiration biopsy recently has been used as a diagnostic modality for selected intraocular tumors and simulating conditions. However, the value of fine-needle aspiration biopsy for intraocular tumors previously has not been clarified. Methods: Transocular fine-needle aspiration biopsy was performed on selected patients who had intraocular lesions that were suspected clinically to be neoplasms but in which there was diagnostic uncertainty based on noninvasive clinical evaluation. These cases were analyzed to determine accuracy, complications, and limitations of the technique. Results: Of 6500 patients referred to the Oncology Service for evaluation of possible intraocular tumor, transocular fine-needle aspiration biopsy was used clinically in 159 cases (2.4%). It proved to be a reliable diagnostic method for intraocular malignancies such as uveal melanoma, uveal metastasis, retinoblastoma, lymphoma, and leukemia. In the 140 cases (88%) in which adequate cytologic material was obtained, the sensitivity rate was 100% and the specificity rate was 98%. In 19 cases where the cytologic material was too scant to render a diagnosis, the sensitivity rate was 84% and the specificity rate was 98%. The problem of insufficient material for cytologic diagnosis has been greatly minimized with the recent use af a 22-gauge needle. The main complication was localized intraocular hemorrhage. Retinal detachment and tumor recurrence have not been observed. Conclusions: Transocular fine-needle aspiration biopsy is a safe and reliable diagnostic method for suspected intraocular tumors and inflammatory conditions in which noninvasive diagnostic modalities have failed to establish the diagnosis and in which cytologic verification of the diagnosis is necessary to institute appropriate treatment. Although the authors have had few complications with fine-needle aspiration biopsy, the technique should be reserved for selected cases where the diagnosis has not been established by less-invasive diagnostic measures. Ophthalmology 1993;100:1677-1684

Medical and Surgical Treatment of Acanthamoeba Keratitis

We examined seven patients with Acanthamoeba keratitis. All patients had a history of soft contact lens use. Predisposing factors included use of homemade saline, hydrogen peroxide disinfection, a history of improper lens care, and swimming with contact lenses. Currently recommended medical therapy, including topical propamidine isethionate and dibromopropamidine isethionate, miconazole, Neosporin, corticosteroids, and systemic ketoconazole, was used in all patients. Five patients have undergone penetrating keratoplasty for progressive primary Acanthamoeba keratitis (four patients) or recurrent infection (one patient) after maximal medical therapy. Two patients who began medical therapy less than three weeks after the onset of symptoms have done well. Early diagnosis of Acanthamoeba keratitis appears critical for successful medical therapy. Penetrating keratoplasty continues to have a central role in the management of more advanced cases that are unresponsive, or only transiently responsive, to medical therapy.

Mechanisms of Maculopathy

This article will review the cellular constituents of the macula and speculate on their contribution to the pathogenesis of macular disease. The retinal pigment epithelium (RPE) has been implicated in senile macular degeneration (SMD). Over time, RPE dysfunction and death may result from the cumulative effect of light and free radical damage. Inherited metabolic abnormalities or the degree of uveal pigmentation could increase the RPEs susceptibility to environmental stress. In exudative SMD, the excessive production of extracellular matrix material by the RPE may contribute to sub-RPE neovascularization and disciform scar formation. Macular edema reflects a breakdown in the blood-retinal barrier. Inflammatory mediators produced in the anterior segment may cause aphakic cystoid macular edema (CME). Recent observations suggest that Müller cell dysfunction is important in CME. Vascular incompetence, as well as capillary occlusion characterize diabetic retinopathy. Angiogenic factors elaborated by ischemic retina are thought to be the stimulus for neovascularization. Diabetic tractional macular detachment results from neovascular proliferation on the partially detached vitreous. Posterior vitreous detachment predisposes to epiretinal gliosis. Endogenous infections and metastatic neoplasms have a predilection for the macula, reflecting the regions high blood flow.