Nora V. Laver

Vitreous evaluation: a diagnostic challenge.

PURPOSE To categorize vitrectomy cytologic diagnoses and ancillary tests to address appropriate processing of low-volume vitreous samples. DESIGN Retrospective case series. PARTICIPANTS Five thousand seven hundred thirty-six vitreous samples. METHODS Cytologic diagnoses of therapeutic and diagnostic vitrectomy samples and their processing protocols from 3 teaching institutions were reviewed. MAIN OUTCOME MEASURES Diagnostic results were categorized as negative for malignancy, suspicious for malignancy, and positive for malignancy. All ancillary studies performed were documented, including special stains, immunohistochemistry analysis, cytokine levels, and polymerase chain reaction (PCR) analysis. RESULTS Of the 5736 vitreous samples analyzed, 4683 (81.64%) were from Tufts Medical Center (TMC), 955 (16.65%) were from Boston Medical Center (BMC), and 98 (1.70%) were from Massachusetts Eye Research and Surgery Institution (MERSI). Cases from TMC and BMC were therapeutic and diagnostic vitrectomies, and MERSI cases were diagnostic vitrectomies. Most vitrectomies showed negative results for malignancy: 99.47% of TMC cases, 99.89% of BMC cases, and 79.6% of MERSI cases. These included vitreous hemorrhage and inflammatory or infectious findings. Ancillary studies performed in this category included Periodic Acid-Schiff staining for fungi, PCR analysis for toxoplasmosis, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex virus I and II, and vitreous cultures for infections (coagulase-negative Staphylococcus, Candida, Fusarium, and Propionibacterium species). Interleukin (IL) 10-to-IL-6 ratios were performed on 38.7% of cases from MERSI. Fourteen cases from TMC were suspicious for malignancy based on cytologic evaluation. Eleven cases from TMC, 1 case from BMC, and 20 cases from MERSI showed positive results for malignancy and included B-cell lymphoma, retinoblastoma, melanoma, and metastatic adenocarcinoma. The ancillary testing included PCR for heavy chain immunoglobulin gene rearrangements, immunohistochemistry for EBV, in situ hybridization for κ and λ light chains, and cytogenetics. CONCLUSIONS This is the largest data pool of reported cytologic diagnoses of diagnostic and therapeutic vitrectomy samples. Cytologic evaluation of therapeutic vitrectomy samples provides a valuable baseline of nonpathologic findings that assist in differentiation between malignancy, infections, and inflammatory conditions. Allocation of small-volume vitreous samples to select ancillary testing from the plethora of available diagnostic tests requires preoperative communication between surgeons and pathologists to ensure appropriate and timely treatment methods.

BEDVH--A method for evaluating biologically effective dose volume histograms: Application to eye plaque brachytherapy implants

PURPOSE A method is introduced to examine the influence of implant duration T, radionuclide, and radiobiological parameters on the biologically effective dose (BED) throughout the entire volume of regions of interest for episcleral brachytherapy using available radionuclides. This method is employed to evaluate a particular eye plaque brachytherapy implant in a radiobiological context. METHODS A reference eye geometry and 16 mm COMS eye plaque loaded with (103)Pd, (125)I, or (131)Cs sources were examined with dose distributions accounting for plaque heterogeneities. For a standardized 7 day implant, doses to 90% of the tumor volume ( (TUMOR)D(90)) and 10% of the organ at risk volumes ( (OAR)D(10)) were calculated. The BED equation from Dale and Jones and published α/β and μ parameters were incorporated with dose volume histograms (DVHs) for various T values such as T = 7 days (i.e.,  (TUMOR) (7)BED(10) and  (OAR) (7)BED(10)). By calculating BED throughout the volumes, biologically effective dose volume histograms (BEDVHs) were developed for tumor and OARs. Influence of T, radionuclide choice, and radiobiological parameters on  (TUMOR)BEDVH and  (OAR)BEDVH were examined. The nominal dose was scaled for shorter implants to achieve biological equivalence. RESULTS  (TUMOR)D(90) values were 102, 112, and 110 Gy for (103)Pd, (125)I, and (131)Cs, respectively. Corresponding  (TUMOR) (7)BED(10) values were 124, 140, and 138 Gy, respectively. As T decreased from 7 to 0.01 days, the isobiologically effective prescription dose decreased by a factor of three. As expected,  (TUMOR) (7)BEDVH did not significantly change as a function of radionuclide half-life but varied by 10% due to radionuclide dose distribution. Variations in reported radiobiological parameters caused  (TUMOR) (7)BED(10) to deviate by up to 46%. Over the range of (OAR)α/β values,  (OAR) (7)BED(10) varied by up to 41%, 3.1%, and 1.4% for the lens, optic nerve, and lacrimal gland, respectively. CONCLUSIONS BEDVH permits evaluation of the relative biological effectiveness for brachytherapy implants. For eye plaques,  (TUMOR)BEDVH and  (OAR)BEDVH were sensitive to implant duration, which may be manipulated to affect outcomes.

Congenital simple hamartoma of the retinal pigment epithelium: clinical, optical coherence tomography, and histopathological correlation

Congenital simple hamartoma of the retinal pigment epithelium: clinical, optical coherence tomography, and histopathological correlation

Loss of tubedown expression as a contributing factor in the development of age-related retinopathy.

PURPOSE Tubedown (Tbdn), a cortactin-binding acetyltransferase subunit, regulates retinal vascular permeability and homeostasis in adulthood. Here the authors explore whether Tbdn loss during aging might contribute to the mechanisms underlying age-related neovascular retinopathy. METHODS A conditional endothelial-specific transgenic model of Tbdn loss was compared with aged mouse and human specimens from 5- to 93-year-old individuals. Specimens were analyzed by morphometric measurements and for functional markers using immunohistochemistry and Western blot analysis. RESULTS An age-dependent decrease in Tbdn expression in endothelial cells of the posterior pole of the eye correlated with pathologic changes in choroidal and retinal tissues of aged mice. In humans, aged specimens without eye disease exhibited a moderate decrease in retinal and choroidal endothelial Tbdn expression compared with younger persons, whereas a greater decrease in choroid vascular Tbdn expression was observed in patients with age-related macular degeneration. In mice, Tbdn loss resulting from old age or conditional Tbdn knockdown was associated with retinal lesions showing significant extravascularly localized albumin and correlated with increased activity of senescence-associated β-galactosidase in the retinal pigment epithelium. A range of abnormalities in RPE, Bruchs membrane, and choriocapillaris observable at the ultrastructural level in Tbdn-knockdown eyes recapitulate those present in human AMD. CONCLUSIONS This work provides evidence that the marked decrease in the level of expression of Tbdn in the retinal and choroidal vasculature during aging contributes to the multifactorial process that leads to the development of age-related retinopathy and choroidopathy.

Epidemiology and Clinical Significance of Ocular Infection

Infection can be the primary cause of ocular tissue damage and visual loss, or it can complicate many types of exogenous injury and systemic or local disease processes. The circumstances associated with the development of ocular infection tend to differ between populations in more economically developed countries and those of less prosperous areas of the world. Countries that are less economically developed may not be able to control endemic infections that cause large-scale visual loss on a population basis. When partial or complete blindness is a relatively common condition in a population, reduced individual productivity can occur that leads to further suppression of economic growth in what is already a resource-poor area. Ocular infection in more developed regions of the world often arises as a preventable complication of contact lens use or ophthalmic surgical procedures or represents a significant form of increased morbidity in patients with systemic diseases that cause immune suppression or vascular compromise. Such infections can contribute to less effective visual rehabilitation and increase the cost of medical care. When assessing any patient, clinical consideration and exclusion of infection is essential. With modern laboratory studies, pathogenic organisms are nearly always classifiable, and effective treatments are available in many cases that can lead to improvement in the patient’s vision and quality of life.

Pathogenic Properties of Infectious Organisms and Tissue Reactions

In spite of an impressive history of progress made by science, medicine, and society as a whole to combat infections, infectious diseases continue to pose new problems. We are threatened by the appearance of new diseases such as Ebola virus and by the reemergence of old ones such as tuberculosis and infection with Streptococcus pyogenes. Pathogens have an impressive adaptability and diversity. Environmental changes, rapid global travel, population movements, and medicine itself through its use of antibiotics and immunosuppressive agents all increase the impact of infections. Infections must be considered in the etiologic differential diagnosis of symptoms affecting any ocular tissue. The major types of infectious agents that cause disease, with examples of specific microbes causing ocular infection, are described in this chapter. A discussion on the human immune system and host defense mechanisms will allow the reader to better understand the different types of inflammation and the cells involved in the process. Infection involves complicated interactions between microbes and hosts, and in most cases, a pathogenic process consisting of several steps is required for an infection to develop. A competent host has a complex array of physical and immunological defenses to prevent infection, and invading pathogens adapt mechanisms to overcome these progressive impediments. Understanding the various modes of invasion among bacteria, viruses, fungi, and parasites, how these agents infect the host and cause damage to tissue, and the host responses to specific infections is the key to better diagnosis and treatment of ocular infections.

Retinal Pigment Epithelial Adenocarcinoma Presenting as an Amelanotic Mass

Retinal pigment epithelium (RPE) neoplasms are extraordinarily rare and have been infrequently described in the literature. Most RPE tumors are pigmented and may simulate choroidal melanoma. The best management of RPE tumors has not yet been elucidated. In the current case, a 36-year-old man presenting with visual disturbance is found to have biopsy-proven RPE adenocarcinoma with subfoveal fluid. He is treated with grid laser over the lesion with complete resolution of fluid. RPE adenocarcinoma can present as an amelanotic mass, and grid laser over the lesion may represent a novel approach for treating associated subretinal fluid.