Ординатура / Офтальмология / Английские материалы / Clinical Pathways in Glaucoma_Zimmerman, Kooner_2001

400 Glaucoma Associated with Systemic Disease

251.Khurana N, Jain S: Cytomorphological spectrum of cysticercosis—a review of 132 cases. Indian J Pathol Microbiol 1999;42:69–71.

252.Abiose A: Onchocercal eye disease and the impact of Mectizan treatment. Ann Trop Med Parasitol 1998;92:S11–S22.

253.Luger MH, Stilma JS, Rigens PJ, et al: In-toto removal of a subretinal Cysticercus cellulosae by pars plana vitrectomy. Br J Ophthalmol 1991;75:561–563.

254.Berche M, Hayot B, Mokrane M, et al: [Ocular cysticercosis, typical forms and treatment]. Ophtalmologie 1990;4:377–379.

255.Schmidt U, Klauss V, Stefani FH: [Unilateral iritis by cysticercal larva in the anterior chamber]. Ophthalmologica 1990;200:210–215.

256.Huismans H: [Intraocular (subretinal) echinococcosis]. Klin Monatsbl Augenheilkd 1977;171: 601–605.

257.Meyer-Schwickerath G: [Echinococcus in the anterior chamber]. Klin Monatsbl Augenheilkd 1973;163:66–70.

258.Williams DF, Williams GA, Caya JG, et al: Intraocular Echinicoccus multilocularis. Arch Ophthalmol 1987;105:1106–1109.

259.Carme B, Kaya-Gandziami G, Pintart D: [Localization of the filaria Loa loa in the anterior chamber of the eye. Apropos of a case]. Acta Trop 1984;41:265–269.

260.Renard G: [Ocular manifestations of loiasis]. J Fr Ophtalmol 1978;1:86.

261.Milligan A, Burns DA: Ectopic cutaneous schistosomiasis and schistosomal ocular inflammatory disease. Br J Dermatol 1988;119:793–798.

262.Kittiponghansa S, Prabriputaloong A, Pariyanonda S, et al: Intracameral anathostomiasis: a cause of anterior uveitis and secondary glaucoma. Br J Ophthalmol 1987;71:618–622.

263.Biswas J, Gopal L, Sharma T, et al: Intraocular Gnathostoma spinigerum. Clinicopathologic study of two cases with review of literature. Retina 1994;14:438–444.

264.Verma VK: Ocular dracontiasis. Int Surg 1968;50:508–509.

265.Joseph A, Raja NSD: Immature stage of Wucheria bancrofti in the human eye. Ind J Ophthalmol 1980;28:89–90.

266.Gupta A, Agarwal A, Dogra MR: Retinal involvement in Wucheria bancrofti filariasis. Acta Ophthalmol (Copenh) 1992;70:832–835.

267.Wang WJ, Xin YJ, Robinson NL, et al: Intraocular paragonimiasis. Br J Ophthalmol 1984;68:85–88.

268.Verin P, Comte P: [A case of ocular paragonimiasis]. Bull Soc Ophtalmol Fr 1984;84:997–999.

269.Harto MA, Rodriguez-Salvador V, Avino JA, et al: Diffuse unilateral subacute neuroretinitis in Europe. Eur J Ophthalmol 1999;9:58–62.

270.De Souza EC, Nakashima Y: Diffuse unilateral subacute neuroretinitis. Report of transvitreal surgical removal of a subretinal nematode. Ophthalmology 1995;102:1183–1186.

271.Goldberg MA, Kazacos KR, Boyce WM, et al: Diffuse unilateral subacute neuroretinitis. Morphometric, serologic, and epidemiologic support for Baylisascaris as a causative agent. Ophthalmology 1993;100:1695–1701.

272.Kuchle M, Knorr HJ, Medenblik-Frysch S, et al: Diffuse unilateral subacute neuroretinitis syndrome in a German most likely caused by the raccoon roundworm, Baylisascaris procyonis. Graefes Arch Clin Exp Ophthalmol 1993;231:48–51.

273.Curtale F, Pezzotti P, Sharbini A, et al: Knowledge, perceptions and behaviour of mothers toward helminths in Upper Egypt: implications for control. Health Policy Plan 1998;13: 423–433.

274.McKerrow JH, Engel JC, Caffrey CR: Cysteine protease inhibitors as chemotherapy for parasitic infections. Bioorg Med Chem 1999;7:639–644.

275.Araujo FG, Khaan AA, Bryskier A, et al: Use of ketolides in combination with other drugs to treat experimental toxoplasmosis. J Antimicrob Chemother 1998;42:665–667.

276.Trouiller P, Olliaro PL: Drug development output from 1975 to 1996: What proportion for tropical disease? Int J Infect Dis 1999;3:61–63.

277.Van der Berg JD, Duvenage CS, Roskell NS, et al: Safety and efficacy of atovaquone and proguanil hydrochloride for the prophylaxis of Plasmodium falciparum malaria in South Africa. Clin Ther 1999;21:741–749.

278.Looareesuwan S, Chulay JD, Canfield CJ, et al: Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group. Am J Trop Med Hyg 1999;60:533–541.

279.Sundar S, Kumar P, Makharia M, et al: Atovaquone alone or with fluconazole as oral therapy for Indian kala-azar. Clin Infect Dis 1998;27:215–216.

280.Browning DJ, Proia AD: Ocular rosacea. Surv Ophthalmol 1986;31:145–158.

281.Forster DJ, Rao NA, Hill RA, et al: Incidence and management of glaucoma in Vogt-Koyanagi- Harada syndrome. Ophthalmology 1993;100:613–618.

282.Tauber J, Melamed S, Foster CS: Glaucoma in patients with ocular cicatricial pemphigoid. Ophthalmology 1989;96:33–37.

283.Liesegang TJ: Conjunctival changes associated with glaucoma therapy: implications for the external disease consultant and the treatment of glaucoma. Cornea 1998;17:574–583.

284.Knox DL: Psoriasis and intraocular inflammation. Trans Am Ophthalmol Soc 1979;77:210–224.

285.Fourman S: Inflammatory glaucoma associated with Sweet’s syndrome. Am J Ophthalmol 1988;105:691–692.

286.Vennos EM, Collins M, James WD: Rothmund-Thomson syndrome: review of the world literature. J Am Acad Dermatol 1992;27:750–762.

287.Lin C, Lueder GT, Kass MA: Ocular abnormalities in a patient with Rothmund-Thomson. J Pediatr Ophthalmol Strabismus 1995;32:132–134.

288.Nathanson M, Dandine M, Gaudelus J, et al: [Rothmund-Thomson syndrome with glaucoma. Endocrine study]. Ann Pedietr (Paris) 1983;30:520–525.

289.Picascia DD, Esterly NB: Cutis marmorata teleangiectatica congenita: report of 22 cases. J Am Acad Dermatol 1989;20:1098–1104.

290.Halmay O, Bajan M, Felden E: Halbseitiges mit Skleroderma assoziiertes Glaukom. Klin Monatsbl Augenheilkd 1968;152:558–562.

291.Stone RA, Scheie HG: Periorbital scleroderma associated with heterochromia iridis. Am J Ophthalmol 1980;90:858–861.

292.Perrot H, Durand L, Thivolet J, et al: [Scleroderma en coup de sabre with homolateral chronic glaucoma]. Ann Dermatol Venereol 1977;104:381–386.

293.Khawly JA, Imami N, Shields MB: Glaucoma associated with the nevus of Ota. Arch Ophthalmol 1995;113:1208–1209.

294.Sears M, Mead A: A major pathway for the regulation of intraocular pressure. Int Ophthalmol 1983;6:201–212.

295.Ten Tusscher MP, Beckers HJ, Vrensen GF, et al: Peripheral neural circuits regulating IOP? A review of its anatomical backbone. Doc Ophthalmol 1994;87:291–313.

296.Waitzmann MB: The hypothalamus and ocular pressure. Surv Ophthalmol 1971;16:1.

297.Honrubia FM, Elliott JH: Efferent innervation of the retina. I. Morphologic study of the human retina. Arch Ophthalmol 1968;80:98–103.

298.Trzeciakowski JP: Central control of intraocular pressure. J Ocul Pharmacol 1987;3:367–378.

299.Yoshizawa T: [New experimental model of central regulation of intraocular pressure]. Nippon Ganka Gakkai Zasshi 1993;97:575–580.

300.Potter DE: Adrenergic pharmacology of aqueous humor dynamics. Pharmacol Rev 1981;33: 133–153.

301.Mapstone R, Clark CV: The prevalence of autonomic neuropathy in glaucoma. Trans Ophthalmol Soc UK 1985;104:265–269.

302.Kumar R, Ahuja VM: Glaucoma and concomitant status of autonomic nervous system. Indian J Physiol Pharmacol 1998;42:90–94.

303.Ziegler D, Haxhiu MA, Kaan EC, et al: Pharmacology of moxonidine, an I1-imidazoline receptor agonist. J Cardiovasc Pharmacol 1996;27:S26–S37.

304.Liu JH, Shieh BE: Suprachiasmatic nucleus in the neural circuitry for the circadian elevation of intraocular pressure in rabbits. J Ocul Pharmacol Ther 1995;11:379–388.

305.Dreyer RF: Ocular hypotony in myotonic dystrophy. Int Ophthalmol 1983;6:221–223.

306.Kuchle M, Naumann GOH, Voelcker HE, et al: [Hypotonia bulbi and gonadotropins in myotonic dystrophy]. Klin Monatsbl Augenheilkd 1988;193:388–392.

307.Walker SD, Brubaker RF: Aqueous humor dynamics in myotonic dystrophy. Invest Ophthalmol Vis Sci 1980;19:140.

308.Chandra V, Bharucha NE, Schoenberg BS: Conditions associated with Alzheimer’s disease at death: case-control study. Neurology 1986;36:209–211.

309.David R, Zangwill L, Briscoe D, et al: Diurnal intraocular pressure variations: an analysis of 690 diurnal curves. Br J Ophthalmol 1992;76:280–283.

This page intentionally left blank

17

Glaucoma Associated with Intraocular Tumors

David J. Bene

Definition

What Is Glaucoma Associated with Intraocular Tumors?

Elevated intraocular pressure (IOP) may be the presenting sign of an intraocular tumor. Typically, this secondary and unilateral glaucoma is dependent on the type, location, and stage of the tumor. The trabecular meshwork can be compromised by several mechanisms resulting in openor closed-angle glaucoma.

What Types of Intraocular Tumors May Be Associated with Glaucoma?

The most common tumors to be associated with glaucoma are uveal melanoma, retinoblastoma, and metastases to the iris, ciliary body, and choroid. Occasional reports of medulloepithelioma, lymphoma, leukemia, systemic hamartosis (neurofibromatosis, oculodermal melanocytosis, and encephalotrigeminal hemangiomatosis), juvenile xanthogranuloma, and nevus of Ota are found in the literature.1–10

When Does One Suspect that Glaucoma Is Secondary to an Underlying Intraocular Tumor?

Intraocular tumor is suspected if there is elevated IOP and asymmetry of the optic nerves. Shields et al2 established 23 mm Hg as the arbitrary lower limit for elevated IOP. A detailed history to elicit the presence of systemic cancer (especially breast, lung, or leukemia), skin lesions (neurofibromas, café-au-lait spots, or nevus of Ota), or buphthalmos may lead to the suspicion of ocular

404 Glaucoma Associated with Intraocular Tumors

involvement. A clinical examination including slit-lamp biomicroscopy, gonioscopy, and indirect ophthalmoscopy may reveal the presence of an atypical mass.

Epidemiology and Importance

What Age Groups Develop Glaucoma Associated with Intraocular Tumors?

There are many intraocular tumors that develop during infancy and childhood that may be associated with glaucoma. Juvenile xanthogranuloma10 is usually apparent in infants and young children. It is rarely seen in adults. It is a benign histiocytic proliferation commonly of the skin with formation of Touton giant cells. However, the iris is the most common extracutaneous site and is frequently associated with hyphema. This tumor is a highly vascularized tan- yellow-to-brown lesion within the iris. Frequently, this is a self-limited tumor that may regress with time.

Retinoblastoma, the most common childhood intraocular malignancy, is associated with inactivation of both alleles of the retinoblastoma gene on the long arm of chromosome 13. Undetected at birth or in adults, retinoblastoma usually presents in unilateral cases at age 23 months and bilaterally at age 1 year.11 The cumulative lifetime incidence of retinoblastoma is approximately 1/15,000 individuals. Inheritance of retinoblastoma can be a result of somatic or germinal factors. However, the majority of retinoblastoma cases are sporadic in nature.12 Histologically, retinoblastomas are recognized by the presence of Flexner-Wintersteiner rosettes. Retinoblastoma has a strong propensity to invade optic nerve, choroid, and scleral emissary canals. Clinically, Ellsworth13 described leukocoria and strabismus as the most frequent initial presentations of retinoblastoma; glaucoma occurred initially in 7% of eyes.

Neurofibromatosis is the most common phakomatosis. This neuroectodemal tumor with autosomal dominant inheritance may involve multiple organs. Neurofibromatosis is classified as type I or type II. Neurofibromatosis type I is peripheral, mapped to chromosome17q11, and is associated with multiple cutaneous café-au-lait spots, presence of optic nerve glioma, multiple Lisch nodules, and inguinal and axiliary freckling.14 Neurofibromatosis type II is central, mapped to chromosome 22q22, and is associated with acoustic neuromas, peripheral nerve sheath tumors, and posterior subcapsular cataracts.15 Neurofibromatosis may present in the first year of life as a congenital glaucoma especially when associated with eyelid involvement or ipsilateral facial hemihypertrophy. François syndrome14 is a type of peripheral neurofibromatosis consisting of unilateral buphthalmos, homolateral facial hemihypertrophy, and homolateral plexiform neuroma of the eyelid.16,17

Medulloepithelioma is a rare congenital tumor typically diagnosed at 2 to 4 years of age, but it may appear in adults as well.18 Clinically, when medulloepithelioma involves the iris, a tan-to-pink mass replaces the normal peripheral iris and invades the angle. In contrast, when medulloepithelioma arises from the ciliary body, a tan-to-white lesion may be observed within the pupil by indirect ophthalmoscopy or slit-lamp examination. Absences of zonules, lens coloboma, and cataract have been associated findings.19 Histologically, this lesion is composed of primitive neuroectodermal cells arising from the non-

pigmented epithelium of the ciliary body. A variety of atypical histologic findings may be present including cartilage and striated muscle.

Nevus of Ota is a unilateral accumulation of melanocytes within the dermis and is associated with ipsilateral pigmentation of the lids and periorbita. This hamartoma is distributed in the ophthalmic and maxillary divisions of the fifth cranial nerve. Pigmentation may be present in the iris, cornea, fundus, optic disc, sclera, and conjunctiva. Most cases are sporadic; however, in some familial cases an autosomal recessive inheritance is present. There is a 4:1 female to male predilection for the occurrence of nevus of Ota.20 The associated glaucoma, more frequent in blacks and Orientals, usually develops in the age group of 20 to 40 years. As shown by Gonder et al,21 whites with nevus of Ota rarely develop glaucoma.

Iris melanocytoma is rare with only incidental case reports in the literature.7,8,21 This benign tumor tends to occur on the inferior iris typically in the fourth decade of life. However, this tumor may undergo malignant transformation. Melanocytomas are frequently present in black or dark-complexioned individuals. Ocular pain, injection, and keratitic precipitates may be the initial presenting signs. Histologically, this tumor is composed of large uniform polygonal cells with small, bland nuclei with intensely pigmented cytoplasm.8 Association with glaucoma has been reported by Shields et al19 in a 23-year-old and by Gonder et al21 in a 7-year-old white girl and in similar patients in their second and third decade of life.21 Croxatto et al22 reported a case of optic disc melanocytoma associated with angle-closure glaucoma in a 44 year old, and there are other reports in the literature.23–25 Iris melanomas usually develop in the fourth decade, whereas most posterior uveal melanomas are diagnosed in patients after the fifth decade.26

Systemic large-cell lymphoma occurs in middle-aged or older patients; it is a form of non-Hodgkin’s lymphoma and is a systemic malignancy. The eye is infrequently involved but can be associated with glaucoma.27 Clinically, large cell lymphoma presents as a bilateral nongranulomatous uveitis that is eventually recalcitrant to topical steroids. Lymphoma cells massively infiltrate the uveal tract and vitreous cavity.

Metastatic tumors are the most common intraocular malignancies. Approximately 10% of patients who die of cancer have evidence of ocular or orbital metastasis, with the choroid being the most common metastatic site.28,29 Metastasis occurs most frequently at ages 40 to 70 from primary cancer of the breast, lung, or gastrointestinal or genitourethral systems.30 However, metastatic cancer may present in children and adults from leukemia. Leonardy et al4 histologically examined the eyes from 135 patients who died of leukemia. Leukemic ocular infiltrates were found in 31.1% of the patients with the choroid as the most frequently involved site. Metastatic tumors may present to the iris but it is rare. Shields et al31 found that of 512 patients with uveal metastasis only 7.8% had iris involvement. Bronchial carcinoid, breast, and lung carcinomas were the most common primary malignancy. These patients complained of blurred vision, redness, and ocular pain. Clinically, iris metastases are fleshy, yellow-white friable masses that release tumor cells into the anterior chamber. It has been reported that the incidence of a secondary glaucoma is 38% with patients in iris metastasis. Iris metastasis is usually seen in adults, but metastatic neuroblastoma is seen in children.31

406 Glaucoma Associated with Intraocular Tumors

What Is the Incidence of Glaucoma Associated with Various Intraocular Tumors?

The association of glaucoma with intraocular tumors was reported as early as 1896 by Marshall.32 The prevalence of tumor-associated glaucoma is largely dependent on tumor type, location, and stage,7,33 as well as on the investigator’s study design. Comparison of various studies produces varied results often dependent on analysis of histologic specimens versus clinical data. Yanoff34 studied the histologic sections of 96 eyes enucleated for melanoma, comparing the 19 eyes with glaucoma (both openand closed-angle forms) to the 77 without glaucoma. His data confirmed the increased risk of glaucoma in large posterior tumors with total retinal detachment, as well as the increased incidence of glaucoma with anterior (iris and ciliary body) melanomas. Ciliary body melanoma alone was not an increased risk factor for glaucoma.

Shields et al2 retrospectively evaluated the intraocular pressure of 2,704 eyes with intraocular tumors that were referred to Wills Eye Hospital from 1974 to 1986. Only those eyes with IOP elevation due to tumor and with pressures greater than 23 mm Hg were included in the study. Only 5% of the eyes with tumors presented with glaucoma (Table 17–1).

UVEAL MELANOMA

Of the 2,111 eyes with uveal melanoma in the series from Shields et al,2 3% had secondary glaucoma: 7% of iris melanomas, 17% of ciliary body melanomas, and 2% of choroidal melanomas. Allaire et al35 and others have described ring melanomas, a rare variant of melanoma involving diffuse, circumferential neoplastic invasion of the iris, ciliary body, and angle. Glaucoma is most often associated with ring melanoma and this secondary glaucoma is a result of direct neoplastic invasion of the chamber angle or neovascularization. Diagnosis of a ring melanoma might be delayed because there is no visible mass on slit-lamp examination, and an intraocular mass may not be detected with B-scan ultrasonography. Heterochromia iridis, increased pigmentation of the trabecular meshwork, and glaucoma are the most frequently reported clinical findings associated with ring melanoma. Although pigmentary dispersion glaucoma and ring melanoma both exhibit increased pigmentation of the trabecular meshwork, pigmentary glaucoma is usually a bilateral process. Krukenberg spindles (pigment on the endothelium) and iris transillumination defects are not clinical signs in ring melanoma.36 Limbal extrascleral nodules may be the first presenting signs of ring melanoma. Ultrasound biomicroscopy may be an important ancillary tool to define this anterior segment tumor. The incidence of ring melanoma is unknown, and therefore the incidence of glaucoma is difficult to determine.35 Studies on the prevalence of glaucoma in uveal melanoma report variable statistics. Some reports are reviews of histologic enucleated specimens versus the incidence of intraocular tumors presenting to a glaucoma or oncology clinic. As Shields et al2 indicate, large melanomas with glaucoma are most likely enucleated by the primary ophthalmologist, and only tumors amenable to irradiation are referred to their institution for further treatment. Recent statistics may also be altered by the widespread use of indirect ophthalmoscopy leading to earlier diagnosis of smaller tumors.

Table 17–1. Eyes with Intraocular Tumors and Secondary Intraocular Pressure (IOP) Elevation

With permission from Shields CL, Shields JA, Shields MB, et al: Prevalence and mechanisms of secondary intraocular pressure elevation in eyes with intraocular tumors. Ophthalmology 1987;94(7): 839–846.

METASTASES

Metastases to the eye most commonly occur to the choroid centrally. In Shields et al’s2 series of 256 eyes manifesting uveal metastases, only 5% developed glaucoma. The majority of these uveal metastases associated with glaucoma involved the iris and ciliary body. Metastases to the iris and ciliary body were less frequent in occurrence but were increasingly associated with glaucoma in 64% and 67% of cases, respectively. In 242 cases of choroidal metastases, only 1% had elevated IOP greater than 23 mm Hg. Iris and ciliary body melanoma have elevated IOP secondary to direct tumor invasion of the angle; choroidal melanoma has elevated IOP resulting in angle closure from choroidal or retinal detachment.2

408 Glaucoma Associated with Intraocular Tumors

LYMPHOMA/LEUKEMIA

Sporadic case reports associate glaucoma with intraocular lymphoma, leukemia, metastatic melanoma, multiple myeloma, histiocytosis X, and myelodysplastic syndrome. In Shields et al’s2 survey, which consisted of 2,704 eyes with intraocular tumors, there were 11 eyes with lymphoma and leukemia each. Glaucoma was associated in 27% and 9% of the eyes with lymphoma and leukemia, respectively.

RETINOBLASTOMA

Reports of glaucoma associated with retinoblastoma vary from 2 to 23%.37,38 In Shields et al’s2 12-year study including 303 eyes with retinoblastoma, 17% developed glaucoma. Elevated IOP usually developed in advanced tumors occupying most of the vitreous cavity.

MEDULLOEPITHELIOMA

Broughton and Zimmerman18 described 56 cases of medulloepithelioma of which 46% were associated with glaucoma. Shields et al’s2 included two medulloepitheliomas among 2,704 intraocular tumors; both cases had elevated IOP.

MELANOCYTOMA

The incidence of melanocytoma complicated by glaucoma is unknown; there are case reports of iris melanocytoma and an even rarer association of optic nerve melanocytoma and glaucoma.8,22

NEUROFIBROMATOSIS

Neurofibromatosis is the most common phakomatosis and its frequency in the general population is approximately one in 3,500.39 Neurofibromatosis type I is more common, and its ophthalmic findings include Lisch nodules, plexiform neurofibromas of the eyelids, diffuse choroidal thickening, prominent corneal nerves, multifocal choroidal nevi, optic nerve gliomas, meningioma, and retinal astrocytic hamartoma. Sachsalber40 described the association of neurofibromatosis and glaucoma as early as 1897.

Congenital glaucoma may be present in patients with neurofibromatosis particularly with plexiform involvement of the eyelid.16 Neurofibromatosis may be associated with partial gigantism or segmentary hypertrophy, especially facial hemihypertrophy. The triad of unilateral buphthalmos, homolateral facial hemihypertrophy, and homolateral plexiform neuroma of the eyelid is known as François syndrome.17 This is the most common presentation of buphthalmos in neurofibromatosis.

NEVUS OF OTA

Case reports of glaucoma associated with nevus of Ota are found in the literature.20 The incidence may be as high as 10% of involved eyes.41