Rene L. Zamora

Distribution of Growth Factors in Subfoveal Neovascular Membranes in Age-related Macular Degeneration and Presumed Ocular Histoplasmosis Syndrome

PURPOSE We performed a histopathologic and immunohistologic study to determine the macromolecular and cellular components of subfoveal neovascular membranes removed at the time of submacular surgery. METHODS Subfoveal neovascular membranes were surgically removed from ten patients (seven with age-related macular degeneration and three with presumed ocular histoplasmosis syndrome). Tissues obtained were examined by light and electron microscopy to identify structural components. Immunohistochemical staining was then performed with monoclonal antibodies to various growth factors, including transforming growth factor-beta 1, basic fibroblast growth factor, platelet-derived growth factor, and epidermal growth factor, as well as antibodies against procollagen 1 and phosphotyrosine residues. RESULTS Most cells in subfoveal neovascular membranes are retinal pigment epithelial cells and cells resembling fibroblasts, with some vascular endothelial cells, lymphocytes, and macrophages. Basic fibroblasts growth factor was found in the extracellular matrix and in endothelial cells. Transforming growth factor-beta 1 was found in endothelial cells, fibroblasts, and retinal pigment epithelial cells. Procollagen 1 was found in protein-synthesizing fibroblasts, and phosphotyrosine residues were detected within fibroblasts, endothelial cells, and retinal pigment epithelial cells. CONCLUSIONS Subfoveal neovascular membranes are neovascular complexes composed of retinal pigment epithelial cells, fibroblasts, vascular endothelial cells, and chronic inflammatory cells. Furthermore, transforming growth factor-beta 1 and basic fibroblast growth factor are present within the major cell types, which suggests a possible pathogenic role in the development of the neovascular complex.

Correlation between Scanning Laser Ophthalmoscope Microperimetry and Anatomic Abnormalities in Patients with Subfoveal Neovascularization

PURPOSE The purpose of the study is to identify the anatomic abnormalities associated with an absolute scotoma and the location and stability of fixation in patients with subfoveal neovascularization in age-related macular degeneration, presumed ocular histoplasmosis syndrome, and other disorders. METHODS Scanning laser ophthalmoscope microperimetry was superimposed on color fundus photographs and fluorescein angiograms of 21 eyes with subfoveal neovascular membranes secondary to age-related macular degeneration (14 eyes) and presumed ocular histoplasmosis syndrome (7 eyes). The authors determined the location and the area occupied by the absolute scotoma and each of the following subretinal lesions: subretinal hemorrhage, neurosensory retinal detachment, retinal pigment epithelial (RPE) atrophy, RPE hyperplasia, atrophy of the choriocapillaris, hard exudates, and the subfoveal neovascular membrane. The area of absolute scotoma determined by scanning laser ophthalmoscope microperimetry was superimposed on the anatomic lesions. The authors calculated the relative risk ratio (RR) of an absolute scotoma occurring in regions corresponding to each anatomic abnormality, and determined the preferred location and stability of fixation in each eye. RESULTS An absolute scotoma was present in areas of chorioretinal scar (RR = 107.61), RPE atrophy (RR = 9.97), subretinal hemorrhage (RR = 2.88), and the neovascular membrane (RR = 1.86). Fixation was stable in all patients with presumed ocular histoplasmosis syndrome but only 29% of patients with age-related macular degeneration. Fifty-five percent of patients with stable fixation fixated over an area of RPE hyperplasia. CONCLUSION The relative risk of an absolute scotoma is highest over areas of chorioretinal scars, RPE atrophy, subretinal hemorrhage, and the neovascular membrane. Fixation is more stable in patients with subfoveal neovascularization from presumed ocular histoplasmosis syndrome than with age-related macular degeneration and frequently is present over an area of RPE hyperplasia.

Branch Retinal Artery Occlusion Caused by a Mitral Valve Papillary Fibroelastoma

PURPOSE We studied clinicopathologically a branch retinal artery occlusion caused by an embolus from a mitral valve papillary fibroelastoma. METHODS At initial examination the patient, a 37-year-old woman, had visual acuity of 20/400 in her left eye, and eight months later her visual acuity improved to 20/20. The diagnosis required echocardiographic and radiologic studies to localize the lesion. RESULTS The mitral valve papillary fibroelastoma was successfully treated with tumor resection involving the mitral valve. CONCLUSIONS It is important to diagnose intracardiac papillary fibroelastoma, because it can cause recurrent arterial embolization and because it responds favorably to tumor resection.

Prediction of occult neck disease in laryngeal cancer by means of a logistic regression statistical model

The ability to accurately predict the presence of subclinical metastatic neck disease in clinically N0 patients with primary epidermoid cancer of the larynx would be of great value in determining whether to perform an elective neck dissection. We describe a statistical approach to estimating the probability of occult neck disease given pretreatment clinical parameters. A retrospective study was performed involving 736 clinically N0 patients with primary laryngeal cancer who were treated surgically with primary resection and ipsilateral neck dissection. Nodal involvement was determined histologically after surgical lymphadenectomy. A logistic regression model was used to derive an equation that calculated the probability of occult neck metastasis based on pretreatment T stage, tumor location, and histologic grade. The model has a sensitivity of 74%, a specificity of 87%, and can be entered into a programmable calculator.

Quantitation of Retinal Ablation in Proliferative Diabetic Retinopathy

PURPOSE We studied 294 eyes of 182 patients, to quantitate the amount of retinal ablation required for regression of proliferative diabetic retinopathy. METHODS Eyes included in the study had two or more proliferative diabetic retinopathy risk factors, received panretinal photocoagulation, and had a minimum follow-up of one year. Laser photocoagulation or cryotherapy was given to eyes that failed to regress or had progression of retinopathy. Eyes treated by other physicians, treated with xenon arc photocoagulation, or undergoing laser treatment or vitrectomy for other retinal conditions were excluded. The total area of retina ablated was calculated and used as a quantitative measure of treatment. RESULTS Regression was observed in 275 eyes (93%); 19 eyes (7%) failed to regress and eventually required vitrectomy. Panretinal photocoagulation alone successfully led to regression in 229 eyes (77%), whereas 46 eyes (15.6%) required both photocoagulation and peripheral anterior retinal cryotherapy. An average of 1.7 treatments per eye led to regression. Eyes were bimodally distributed by requirement for treatment, into low and high treatment groups. Low treatment eyes received an average of 510 mm2 of retinal ablation (2,600 500-microns burns), and high treatment eyes, 1,280 mm2 (6,500 500-microns burns). More extensive treatment was required with more retinopathy risk factors (P = .002 for four vs three risk factors and P = .0007 for four vs two risk factors); duration of diabetes mellitus longer than 15 years (P = .004), and onset of diabetes mellitus before 30 years of age (P = .0008). CONCLUSION Patients with proliferative diabetic retinopathy should be treated aggressively with panretinal photocoagulation, cryotherapy, or both. The amount of initial treatment required for regression may be considerably more than that recommended by the Diabetic Retinopathy Study.

Multiple Recurrent Branch Retinal Artery Occlusions Associated With Varicella Zoster Virus

Purpose: The authors describe an immunocompetent patient who developed multiple recurrent branch retinal artery occlusions (BRAOs) associated with the varicella zoster virus (VZV). Methods: A 69-year-old woman with mild bilateral vitritis developed superior and inferior BRAOs in her right eye with decreased visual acuity to 20/40, and a peripheral BRAO inferotemporally in her left eye. One month later, the inferotemporal BRAO progressed proximally in her left eye with a decrease in visual acuity to 20/40. After an extensive negative systemic evaluation, she underwent a diagnostic pars plana vitrectomy of her right eye. Results: Vitreous fluid was positive for VZV DNA by polymerase chain reaction (PCR). The patient was treated with intravenous acyclovir and systemic oral steroids. After remaining disease free for 3 months, the patient had two recurrences: 1) a mild vitritis and 2) development of a new superior temporal artery occlusion in the left eye. Both recurrences were treated with oral acyclovir and systemic steroids. The patient remained recurrence free for 12 months on a maintenance dose of oral acyclovir, and for 4 additional months without acyclovir. Conclusions: Varicella zoster virus can be associated with the syndrome of multiple recurrent BRAOs. The diagnosis of VZV-associated BRAO can be established by PCR of intraocular fluid.

Clinical staging for primary malignancies of the supraglottic larynx

A study of 520 patients with primary supraglottic cancer was conducted. The tumors were staged according to the 1983 and 1988 American Joint Committee on Cancer (AJCC) T‐and N‐stage definitions. There were 293 patients with early stage (T1, T2) tumors, 227 with advanced stage (T3, T4) tumors and 428 with early nodal disease (N0, N1) in both systems. In the 1983 N‐staging, there were 44 N2 and 48 N3 lesions; in the 1988 N‐staging, there were 62 N2 and 30 N3 lesions. Cox regression analysis showed that the 1983 and 1988 T‐stage (T1 through T4) definitions successfully prognosticate for survival when patients were without neck node involvement. In contrast, when neck nodes were present, the N‐stage (N0 through N3) of the disease prognosticated survival better than T‐stage. Further analyses showed that the 1988 N‐stage definition provided a better separation between N2 and N3 lesions compared to the 1983 version. Combined‐modality treatment (surgery and radiation) significantly improved survival compared to single‐modality treatment (surgery or radiation alone) when patients were staged T4 and N0 through N3 neck disease, but not when patients advanced from T1 to T3. Comparison of treatment efficacy over the last four decades for single‐and combined‐modality treatment did not reveal statistically significant differences in survival rates in our patient population. This was consistent with cumulative results of various institutions over the last four decades. We conclude that the 1988 AJCC T‐and N‐stage definitions successfully prognosticate for T‐stage (T1 through T4) and N‐stage (N0 through N3) with better separation of N2 and N3 lesions compared to the 1983 version.

Epidermoid carcinoma of the oral cavity and oropharynx: validity of the current AJCC staging system and new statistical tools for the prediction of subclinical neck disease.

The 1983 and 1988 AJCC T- and N-staging systems were compared using the case records of 531 patients with primary epidermoid malignancies of the oral cavity. All patients had a minimum followup of 5 years. There were 390 patients with early stage (T1, T2) disease and 141 with advanced stage (T3, T4) lesions according to both the 1983 and 1988 T-definitions: 342 patients manifested no clinical nodes (NO), 189 had clinically evident nodes (N1-N3), and none had metastatic disease. Cox regression analysis demonstrated that the 1983/1988 T-stage definitions differentiated survival successfully (p < 0.001). The 1988 staging system for nodal disease showed a highly significant separation of N2 and N3 when compared with the 1983 system (p < 0.001). Of the 342 patients who were staged NO, 154 had primary neck dissection. Logistic regression predicted the incidence of subclinical disease according to the site and the T-stage of the primary tumor with a sensitivity of 78% and a specificity of 95%. We conclude that the 1988 N-stage definition is a better prognosticator of survival than the 1983 definition. Furthermore, a logistic regression model can be used to predict the probability of subclinical disease in primary oral cavity cancers.

Clinical classification and staging for primary malignancies of the maxillary antrum

A study of 51 patients with primary malignant maxillary sinus neoplasms was conducted. None of the patients had neck nodes and/or metastases, and each had 5‐year follow‐up. The tumors were staged according to the 1983 and 1988 American Joint Committee on Cancer staging systems for maxillary sinus cancers. There were 13 early stage (T1, T2) and 38 advanced (T3, T4) tumors in both systems. Cox regression analyses of survival curves showed increasingly worse prognoses for advanced tumors in both T‐staging systems. Further analyses showed a significant difference in survival between T3 and T4 in the 1988, but not in the 1983 system. There were no significant differences in survival according to treatment modality or histological type of malignancy. We conclude that the 1988 system prognosticates successfully for T‐stage (1 to 4) and demonstrates significant improvement in detecting T3 versus T4 differences compared to the 1983 system. The 1988 system applies equally for epidermoid cancer and other malignancies of the antrum.