Ehud Zamir

Neoplastic Masquerade Syndromes

Masquerade syndromes are classically defined as entities which emulate inflammatory conditions but which are in fact due to a neoplastic process. Careful history and examination in concert with appropriate ancillary investigations and histopathologic evaluation of tissue specimens are required in order to make the correct diagnosis. Many conditions may result in an appearance mimicking an inflammatory condition. The authors review neoplastic conditions which may be considered masquerades. The most common of these is primary intraocular lymphoma or primary central nervous system lymphoma, occurring predominately in older individuals. Diagnostic strategies, therapy, and prognosis are reviewed in detail. Other conditions that can be considered masquerade syndromes are reviewed as well, including lymphomatous and nonlymphomatous conditions, such as melanoma, retinoblastoma, juvenile xanthogranuloma, metastatic lesions, and paraneoplastic syndromes, among others.

Proliferative activity and p53 expression in primary and recurrent pterygia

PURPOSE To assess p53 expression and proliferative activity in primary and recurrent pterygia from the same eyes. DESIGN Retrospective comparative human tissue study. PARTICIPANTS Tissue from excised primary pterygia that did not recur (group A, n = 10) was compared with tissue from primary pterygia that recurred (group B, n = 10) and to the recurrent pterygia tissue that was excised from subjects in group B (group C, n = 10). Ten normal conjunctivas served as controls (group D). METHODS Sections from each pterygium were immunostained with the MIB-1 and bp53. 12 monoclonal antibodies that react with Ki-67 and p53 antigens, respectively. MAIN OUTCOME MEASURES Proliferative activity was calculated as the mean of the MIB-1 positive cell count per eyepiece grid in high magnification (x40) (positive cell count/grid). Percentage of positive cells of all cells in the grid area was evaluated in the p53-stained sections. RESULTS Proliferative activity was found in the epithelium overlying the pterygia and normal conjunctiva. The mean MIB-1 positive cell count/grid +/- standard error was 2.84 +/- 1.07, 1.74 +/- 0.82, 3.83 +/- 1.35, and 0.86 +/- 0.33 in groups A, B, C, and D, respectively (P = 0.17, Kruskal-Wallis). P53 staining was found in 50% of pterygia in groups A, B, and C; none of the normal conjunctival tissues showed p53 immunoreactivity. Four of five p53-positive tissues in group B were p53-negative in group C. In the p53-positive pterygia, less than 10% of cells were p53 positive. However, p53-positive pterygia had higher mean MIB-1 positive cell count/grid +/- standard error as compared with the p53-negative lesions, 4.56 +/- 0.94 vs 1.39 +/- 0.59 (P = 0.021, Mann-Whitney). CONCLUSIONS p53 immunoreactivity and high proliferative activity in the epithelium overlying the pterygium are not associated with recurrence of pterygium.

A prospective evaluation of subconjunctival injection of triamcinolone acetonide for resistant anterior scleritis.

PURPOSE Prospective evaluation of the efficacy and safety of subconjunctival triamcinolone injections for resistant, nonnecrotizing, anterior scleritis. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS Twelve eyes of 10 consecutive patients seen in the Doheny Eye Institute between August 1999 and December 2000 with diffuse, nonnecrotizing anterior scleritis that was resistant to systemic antiinflammatory therapy. Eyes with a history of steroid response were excluded. INTERVENTION Subconjunctival injection of triamcinolone acetonide to the areas of maximal inflammation. MAIN OUTCOME MEASURES Scleritis activity, adverse treatment effects, and number of systemic medications required at the end of the follow-up period. RESULTS Within 1 to 14 days after injection, complete resolution of signs and symptoms was achieved in 11 eyes and partial resolution in 1 eye. Two patients had one recurrence each, 2.5 and 11 months after injection. Six of 10 patients were able to discontinue all systemic therapy (prednisone +/- immunosuppressive drugs); the remaining 4 needed continued oral therapy for systemic indications. Transient ocular hypertension and subconjunctival hemorrhage occurred in one eye each. Median follow-up period was 15 months. No eye developed necrotizing scleritis. CONCLUSIONS Subconjunctival injection of triamcinolone acetonide is a safe and effective treatment for resistant, nonnecrotizing anterior scleritis. It provides rapid effect, is well tolerated, and may spare patients the significant complications and side effects of systemic corticosteroid and immunosuppressive therapy.

Long-Term, Multicenter Evaluation of Subconjunctival Injection of Triamcinolone for Non-Necrotizing, Noninfectious Anterior Scleritis

PURPOSE We sought to characterize the long-term outcomes and complications of subconjunctival triamcinolone acetonide injection (STI) for non-necrotizing, noninfectious anterior scleritis. DESIGN Retrospective, interventional, noncomparative, multicenter study. PARTICIPANTS Sixty-eight eyes of 53 patients from 9 participating hospitals in the United States, Singapore, and Australia. Only eyes with 6 or more months of follow-up were included. INTERVENTION Subconjunctival injection of 2 to 8 mg of triamcinolone acetonide was administered to eyes with non-necrotizing, noninfectious anterior scleritis. MAIN OUTCOME MEASURES Resolution of signs and symptoms, time to recurrence of scleritis, and side effect profile. RESULTS Median follow-up was 2.3 years (range, 6 months to 8.3 years). Sixty-six eyes (97.0%) experienced improvement of signs and symptoms after 1 injection. Twenty-four months after a single injection, 67.6% of eyes remained recurrence-free, whereas at 48 months, 50.2% were recurrence-free. Some 55.0% of patients who had adverse effects from systemic medications were off all systemic medications at last follow-up; 55.0% of patients who were taking systemic medications at the time of first triamcinolone acetonide injection were not taking prednisone and immunosuppressants at this time; 76.2% of patients still requiring systemic agents had associated systemic disease. Fourteen eyes (20.6%) had ocular hypertension not requiring intraocular pressure (IOP)-lowering therapy. Two eyes (2.9%) were treated with topical IOP-lowering agents alone, and 2 eyes required surgical intervention for glaucoma. None developed scleral necrosis or melt. CONCLUSIONS This retrospective, international study carried out at 9 hospitals suggests that STI can treat non-necrotizing, noninfectious anterior scleritis with side effects limited to elevated IOP in a few patients. Although no cases of scleral melt or necrosis were observed, we cannot definitively conclude that this may not occur after STI. Intraocular pressure should be closely monitored after STI. Subconjunctival triamcinolone acetonide injection may be useful as adjuvant therapy or to decrease systemic medication burden. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Massive mycobacterial choroiditis during highly active antiretroviral therapy: another immune-recovery uveitis?

PURPOSE To describe the ocular presentation of disseminated mycobacterial disease occurring during immune-recovery in a patient with acquired immune deficiency syndrome (AIDS). STUDY DESIGN Case report and literature review. PARTICIPANTS A 41-year-old AIDS patient with a prior diagnosis of cytomegalovirus retinitis. METHODS The patient developed progressive, bilateral multifocal choroiditis with panuveitis 2 months after beginning and responding to highly active antiretroviral therapy. His left eye became blind and painful and was enucleated. Pathologic examination revealed massive choroiditis with well-formed, discrete granulomas and multiple intracellular and extracellular acid-fast organisms within the choroidal granulomas. Culture and polymerase chain reaction of vitreous specimens revealed Mycobacterium avium complex (MAC). RESULTS Empiric, and later sensitivity-guided, local and systemic antibiotic therapy was used to treat the remaining right eye, but it continued to deteriorate. Despite medical therapy, three vitrectomies and repeated intravitreal injections of amikacin, a total retinal detachment ensued. One week after the third vitrectomy, the patient died from mesenteric artery thrombosis in the setting of disseminated mycobacterial disease. CONCLUSIONS This is the first report of ocular inflammation as the presenting finding in the recently recognized syndrome of immune-recovery MAC disease. Pathogenesis of this entity is related to an enhanced immune response to a prior, subclinical, disseminated infection. The formation of discrete granulomas, normally absent in MAC infections in AIDS, reflects this mechanism.

Rhabdomyomatous mesenchymal hamartoma of the eyelid: report of a case and literature review.

PURPOSE To report a rare case of rhabdomyomatous mesenchymal hamartoma and to compare its features with those cases previously reported. DESIGN Interventional case report and literature review. INTERVENTION Complete ophthalmologic and systemic examinations followed by excisional biopsy and histopathologic examination. MAIN OUTCOME MEASURES Clinical examination features and histopathologic findings. RESULTS A 6-month-old Latino male presented with a congenital, elevated, smooth, flesh-colored right lower eyelid lesion. An ipsilateral right limbal dermoid and an upper eyelid coloboma were also present. Excisional biopsy of the eyelid lesion revealed randomly oriented mature striated muscle tissue with associated adipose tissue, blood vessels, pilosebaceous units, and peripheral nerves, findings consistent with rhabdomyomatous mesenchymal hamartoma. Of the 24 reported cases (including the current case), eight had associated congenital anomalies. CONCLUSIONS Although rhabdomyomatous mesenchymal hamartomas are rare and benign, they may be associated with other congenital anomalies and anomaly syndromes. As a result, we recommend systemic evaluation of patients diagnosed with this entity.

Syphilitic Punctate Inner Retinitis in Immunocompetent Gay Men

PURPOSE To describe the features of an unusual syphilitic uveitis syndrome in a cluster of homosexual patients. DESIGN Retrospective case series. PARTICIPANTS Five consecutive patients diagnosed with syphilitic retinitis in our Melbourne uveitis clinic over a period of 8 months. METHODS The case notes of patients diagnosed with syphilitic retinitis were reviewed and the clinical features are presented and discussed. MAIN OUTCOME MEASURES Description of retinal findings and documentation of any associated sequelae. RESULTS All patients were homosexual men. Two were human immunodeficiency virus positive. None of the patients had been previously diagnosed with syphilis, although 3 presented with systemic symptoms and signs of secondary syphilis. All patients had marked anterior uveitis and vitritis. All patients had acute retinal arteriolitis and inner retinitis, with distinctive, inner retinal and preretinal white dots. These retinal findings were remarkably similar in all patients, and resolved with little or no sequelae after standard systemic treatment for syphilis, combined with oral prednisolone. CONCLUSIONS Syphilitic retinitis may be an increasingly common clinical problem, reflecting the growing incidence of syphilis among homosexual men in Australia. Our patients showed stereotypical ocular and systemic features, which are useful in differentiating this condition clinically from other types of acute posterior uveitis, such as necrotizing viral retinitis. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Microglial stability and repopulation in the retina.

Background/aims: Parenchymal central nervous system microglia are repopulated by bone marrow derived monocytes more slowly than any other reticuloendothelial cells. The contribution of bone marrow derived monocytes to the uninflammed retina has not been studied. The present study sought to determine repopulation of retinal microglia in uniflammed retina by bone marrow derived monocytes in bone marrow chimeric rats. Methods: Chimeric (Y→X) Lewis rats were constructed by transplanting 5×107 male bone marrow cells into lethally irradiated female recipient rats. The chimeras were sacrificed 8, 10, 12, 30, and 52 weeks after bone marrow transplant, and retina, brain, lung, and spleen samples were collected. DNA was extracted and quantified. Y positive infiltrating cells in the collected samples were detected by polymerase chain reaction amplification of a Y chromosome specific 104 bp fragment. Results: There was a rapid repopulation of haematopoietic tissues in the spleen (at 8 weeks), confirming the establishment of chimerism, and to a lesser extent, of lung (at 30 weeks). This repopulation was absent in the brain parenchyma and retina until 52 weeks after transplantation. Conclusions: These data indicate that resident microglia in the retina, much like those in the brain, are stable in number in the retinal compartment (up to 1 year), and repopulation by bone marrow derived cells may be delayed for a year.

Conjunctival ulcers in Behçet's disease

PURPOSE To describe the occurrence of conjunctival ulcers as a manifestation of Behçets disease. DESIGN Retrospective, noncomparative, interventional case series with histopathologic correlation. METHODS Six patients who fulfilled the diagnostic criteria for Behçets disease and presented with painful conjunctival ulcers were included in the study. Three of these ulcers were biopsied and studied histologically and immunohistochemically. The lesions were treated with topical or subconjunctival injection of corticosteroids and, in one case, with oral indomethacin. RESULTS Although all six patients fulfilled the diagnostic criteria for Behçets disease, two developed uveitis and other signs of Behçets disease only months to years after the appearance of the conjunctival ulcers. The 3- to 5-mm, round to oval ulcers were located in the limbal and/or bulbar conjunctiva. Histopathology revealed disrupted epithelium, infiltration of both acute and chronic inflammatory cells, and high endothelial venules. Immunohistochemical analysis of the infiltrating lymphocytes revealed primarily T-cell populations admixed with several B cells and CD68-positive histiocytes. After treatment, the conjunctival lesions invariably healed without scarring. CONCLUSIONS In addition to the oral and genital ulceration, ulcers can also be found in the conjunctiva of patients with Behçets disease. Although this is a rare clinical sign, when accompanied by uveitis or orogenital ulcers, it may suggest a diagnosis of Behçets disease.

Juvenile xanthogranuloma masquerading as pediatric chronic uveitis: a clinicopathologic study.

Juvenile xanthogranuloma (JXG) is a rare, pediatric histiocytic skin disorder that may affect the eye. It can present with protean ocular manifestations, including masquerade uveitis, heterochromia, hyphema, or glaucoma. It very rarely involves the retina and posterior segment; indeed, posterior involvement has been documented histopathologically in only one case. We present the case of a 2-year-old child with ocular JXG presenting as chronic, refractive uveitis, without skin or systemic findings. The blind, painful eye was enucleated and found to harbor a diffuse histiocytic process that involved both the anterior and posterior segments, including the retina and subretinal space. Histological, immunohistochemical, and electron microscopic studies confirmed the diagnosis of JXG. The pathologic classification and differential diagnosis of systemic histiocytic disorders are discussed. Since JXG can present as masquerade pediatric uveitis, this entity should be considered in children with atypical uveitis. In rare instances, JXG may involve the posterior segment and the retina, leading to retinal detachment and blindness.