Ch 7. Eales Disease of the Retina

EALES’ DISEASE

Eales’ disease was initially described in young males with vitreous hemorrhage and abnormal retinal veins.[59] Now it is clinically defined by an obliterative vasculopathy involving both venules and arterioles (Figure 7-9).[60] In the late stages, ischemia leads to neovascularization with resulting vitreous hemorrhage, retinal detachment, and secondary glaucoma.[61][62] Specimens are obtained when vitrectomy is done to remove persistent vitreous hemorrhage or extraretinal fibrous tissue.[63] Cytologic specimens may show vitreous hemorrhage (hemoglobin spherulosis) and, occasionally, fibrous tissue (Figure 7-10).
Other conditions that produce neovascularization and vitreous hemorrhage include branch retinal vein occlusion,[64] sickle cell retinopathy,[65] carotid and aortic arch occlusive syndromes,[66] and hyperviscosity syndromes.[67]
References:
59. Eales H. Cases of retinal hemorrhage associated with epistaxis and constipation. Birm Med Rev 1880;9:262.
60. Elliot AJ. Thirty-year observation of patients with Eales' disease. Am J Ophthalmol 1975;80:404-408.
61. Renie WA, Murphy RP, Anderson KC, Lippman SM, McKusick VA, et al. The evaluation of patients with Eales' disease. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1975;194:73-85.
62. Spitznas M, Meryer-Schwickerath GT, Staphan B. The clinical picture of Eales' disease. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1975;194:73-85.
63. Gieser SC, Murphy RP. Eales' disease. In: Ryan SJ, Schachat AP, Murphy RP, Patz A, eds. Retina. St. Louis: C.V. Mosby, 1989;2:535-540.
64. Heyreh SS, Rojas P, Podhajsky P, Montague P, Woolson RF. Ocular neovascularization with retinal vein occlusion. Ophthalmology 1983;20:488-506.
65. Goldberg MF. Classifcation and pathogenesis of proliferative sickle retinopathy. Am J Ophthalmol 1971;71:649-665.
66. Kahn M, Green WR, Knox DL, MIller NR. Ocular features of carotid occlusive disease. Retina 1986;6:239-252.
67. Ring CP, Pearson TC, Sanders MD, Wetherly Mein G. Viscosity and retinal vein thrombosis. Br J Ophthalmol 1967;60:397-410.

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Diabetic Retinopathy, Coats Disease, Proliferative Vitreoretinopathy

COATS’ DISEASE

Coats’ disease is usually unilateral and is characterized by exudative retinal detachment in young males.[19][20][21] Telangiectatic blood vessels have been identified in this disorder and presumably are the basis for the retinal exudates and exudative detachment of the retina (Figure 7-3).[22][23] Coats’ disease may produce leukocoria in children and can be confused clinically with retinoblastoma. In such cases, a fine needle aspiration may be obtained to differentiate these two entities. In addition, a vitrectomy may be employed to repair the retinal detachment.[24][25][26] In either case, the specimens are extremely hypocellular with occasional macrophages containing cytoplasmic vacuoles (Figure 7-4).[27] Histologically, there is massive subretinal exudates and retinal detachment. Telangiectasis of the retinal blood vessels or the extraretinal blood vessels can be identified (Figure 7-5).

DIABETIC RETINOPATHY

Diabetic retinopathy is the single most common source of intraocular washing specimens processed by our cytology laboratory. Retinopathy occurs in about 70% of patients who have had diabetes mellitus beyond 20 years. Diabetic retinopathy manifests as a microangiopathy with thickening of vascular basement membrane, loss of endothelium, and degeneration of capillary pericytes.[28][29][30][31][32] In the early stages, venous dilatation, capillary microaneurysms, and exudates are observed.[33][34] Vascular disease leads to ischemia of the retina and neovascularization is stimulated (proliferative diabetic retinopathy) (Figure 7-6).[35][36] Vitrectomy may be performed in this disease for several reasons, including vitreous hemorrhage secondary to neovascularization and tractional retinal detachment with removal of fibrovascular membrane.[37][38][39]
Neovascularization is identified in vitrectomy specimens as well-defined blood vessels lined by a single layer of endothelium (Figure 7-7).

PROLIFERATIVE VITREORETINPATHY

The leading cause of failure in retinal detachment surgery is proliferative vitreoretinopathy (PVR).[40][41][42][43] It is characterized by a proliferation of cellular membranes on both sides of the detached retina and in the vitreous cavity.[44] Fibrovascular proliferation that extends anterior to the posterior border of the vitreous base has been termed anterior PVR.[45] Traction induced from the membranes on the posterior lens surface, ciliary body, and iris may produce a peripheral retinal detachment.[46] Epiretinal membranes are composed of retinal pigment epithelial cells, glial cells, fibrocytes, and macrophages.[47][48][49][50][51][52][53][54][55][56] Surgically removed epiretinal membranes may be sent for cytologic examination. Cell buttons or cytospin preparations reveal a thin fragment composed of spindle cells and oval cells, some of which may contain pigment (Figure 7-8).
Epiretinal membranes composed mainly of spindle cells have been associated with photocoagulation, trauma, and inflammatory disease.[57] However, most simple epiretinal membranes are idiopathic.[58]
References:
19. Coats G. Royal London Ophthal Hosp Rep 1908;17:440-525.
20. Fox KR. Metabol Pediatr Syst Ophthalmol 1980;4:121-124.
21. Reese AB. Am J Ophthalmol 1956;42:1-8.
22. Chang M, McLean IW, Merritt JC. J Pediatr Opthalmol Strabismus 1984;21:163-168.
23. Egbert PR, Chan CC, Winter FC. J Pediatr Ophthalmol 1977;13:336-339.
24. Jaffe MS, Shields JA, Canny CLB, Eagle RC, Fry RL. Ann Ophthalmol 1977;9:863-868.
25. Pe'er J. Am J Opthalmsol 1988;106:742-743.
26. Laqua H, Wessing A. Ophthalmology 1983;90:1284-1291.
27. Haik BG, Koizumi J, Smith ME, Ellsworth, RM. Am J Opthalmol 1985;100:327-328.
28. Robison WG Jr. Kador PF, Kinoshita JH. Science 1983;221:1177.
29. Kalebic T, Garbisa S, Glaser B, Liotta LA.Science 1983;221:281.
30. Kuwabara T, Cogan DG. Arch Ophthalmol 1963;69:492-502.
31. Toussaint D, Dustin P. Arch Ophthalmol 1963;70:96-108.
32. Yanoff M. N Engl J Med 1966;274:1344-1349.
33. De Venecia G, Davis M, Engerman R. Arch Ophthalmol 1976;94:1766-1773.
34. Addison DJ, Garner A, Ashton N. Br Med J 1970;1:264-266.
35. Niki T, Muraoka K, Shimizu K. Ophthalmology 1984;91:1440.
36. Miller H, Miller B, Zonis S, Nir I. Invest Ophthalmol Vis Sci 1984;25:1338-1342.
37. Thompson JT, de Bustros S, Michels RG, Rice TA. Arch Ophthalmol 1987;105:503-507.
38. Thompson JT, de Buustros Michels RG, Rice TA. Arch Ophthalmol 1987; 105:191-195.
39. Blankenship GW. St Louis: C.V. Mosby, 1989;3:515-539.
40. The Retinal Society Terminology Committee. Ophthalmology 1983;90:121-125.
41. Claes C, Freeman HM, Tolentino FI. New York: Springer-Verlag, 1988:3-11.
42. Lewis H, Aaberg TM, Abrams GW. Am J Ophthalmol 1991;111:8-14.
43. Schwartz D, De la Cruz ZC, Green WR, Michels RG. Retina 1988;8:275-281.
44. Glaser BM. Pathobiology of PVR. New York: Springer-Verlag, 1988:12-21.
45. Lewis H, Aaberg T. Am J Ophthalmol 1988; 105:277.
46. Lewis H, Abrams GW, Foos RY. Am J Ophthalmol 1987;104:614-618.
47. Machemer R, Laqua H. Am J Ophthalmol 1975;80:1-23.
48. Clarkson JG, Green WR, Massoff D. Am J Ophthalmol 1977;84:1-17.
49. Daicker B, Guggenheim R. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1979;210:109-110
50. Van Horn DL, Aaberg TM, Machemer R. Am J Ophthalmol 1977;84:383-393.
51. Kampik A, Kenyon KR, Michels RG, Green WR, de Cruz ZC, Epiretinal and vitreous membranes: comparative study of 56 cases. Arch Ophthalmol 1981;198199:1445-1454.
52. Kampik A, Green WR, Michels Rg, Nase PK. Ultrastructure of progressive idiopathic epiretinal membrane removed by vitreous surgery. Am J Ophthalmol 1980:90:797-809.
53. Hiscott PS, Grierson I, McLeod D. Natural history of fibrocellular epiretinal membranes: a quanative, autoradiographic and immunohistochemical study. Br J Ophthalmol 1985;69:810-823.
54. Michels RG. A clinical and hisopathical study of epiretinal membranes affecting the macula and removed bu vitreous surgery. Trans Am Ophthalmol Soc 1982;80:580-656.
55. Foos RY. Spectrum of nonvasular proliferative extraretinopathies. In: Nicholson DH, ed. Ocular pathology update. New York: Masson Publishing, 1980:107-114.
56. Foos RY. Nonvascular proliferative extraretinopathies. Am J Ophthalmol1978;86:723-725.
57. Kampik A, Green WR, Michels RG, Rice TA. Epiretinale membranen nack photokoagulation (postkoagulative maculopathie). Ber Dtsch Ophthalmol Ges 1981;78:593-598.
58. Roth AM, Foos RY. Surface wrinking retinopath in eyes enucleated at autotopsy. Trans AM Acad Ophthalmol Otolaryngol 1971;75:1047-1058.

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CHAPTER 7 Retinopathy of Prematurity

Abnormalities of the Retina

Our goal in this chapter is to introduce those retinal diseases that are most commonly encountered in cytology specimens. The diagnosis of many of these lesions by cytologic techniques alone can be difficult and thorough familiarity with the tissue lesion can be very helpful.
The ocular cytologist is likely to encounter specimens from only a few retinal diseases on a routine basis. Intraocular washings from patients with diabetic retinopathy and proliferative vitreoretinopathy account for most of the specimens. Because the diagnosis is often apparent from clinical examination, some argue that it is superfluous to send the intraocular washings for pathologic examination. Indeed, only 15% of intraocular washings are diagnostic of specific diseases.[1] However, the need to exclude clinically unsuspected infectious and neoplastic disorders justifies routine processing of vitrectomy specimens. Examination of intraocular washings sometimes reveals retinal fragments. It is often difficult to diagnose specific diseases from retinal fragments seen in cytologic preparations. Other accompanying fragments usually provide clues to the diagnosis. Notable exceptions in which diseases are diagnosed by retinal biopsies include infectious retinitis and retinoblastoma. These entities are discussed separately in Chapters 8 and 9, respectively.

RETINOPATHY OF PREMATURITY

Previously called retrolental fibroplasias,[2] retinopathy of prematurity is a disease of the premature infant.[3] It is usually, but not always, associated with exposure to high concentration of oxygen.[4][5][6][7] The natural history and pathogensis of these diseases is discussed in detail elsewhere.[8][9][10][11] In brief, retinopathy of prematurity develops at the border of the developing retinal vasculature.[12][13] Presumably, ischemia leads to proliferation of the primitive microvasculature, which in turn may lead to tractional retinal detachment (Figure 7-1).[14][15]
Vitrectomies are preformed in the late stages to remove the vitreous and fibrovascular tissue in order to repair the retinal detachment.[16][17] When the retina is detached, the visual prognosis is poor.[18] In cytologic preparations, fibrous tissue, lens fragments (lensectomy), pigment-laden macrophages, and vitreous hemorrhage can be observed (Figure 7-2). These findings are not specific for retinopathy of prematurity.
References:
1. Green WR. Ophthalmology 1984;91:726-749.
2. Foos RY. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1975;195:87-100.
3. Keith CG, Kitchen WH. Med J Aust 1984;141:225-227.
4. Patz A. Am J Ophthalmol 1985;100:164-168.
5. Kushner BJ, Gloeckner E. Am J Ophthalmol 1984;27:148-163.
6. Shohat M, Reisner SH, Krikler R, Nissonkorn I, Yassur Y, et al. Pediatrics 1983;72:159-163.
7. Karlsberg RC, Green WR, Patz A. Arch Ophthalmol 1973:89:122-123.
8. Flynn JT, Bancalari E, Bachynski BN, Buckley EB, Bawd R, et al. Ophthalmology 1987;94:620-629.
9. Prendiville A, Schulenberg WE. Arch Dis Child 1988;63:522-527.
10. Silverman WA, Flynn JT. Boston: Blackwell Scientific, 1985.
11. McPherson AR, Hittner HM, Kretzer FL. Toronto: B.C. Decker, 1986.
12. Foos RY. Retina 1987;7:260-276.
13. Kushner BJ, Essner D, Cohen IJ, Flynn JT. Arch Ophthalmol 1977;95:29-38.
14. Campbell FW. Trans Ophthalmol Soc UK 1951;71:287-300.
15. Quinn GE, Schaffer DB, Johnson L. Am J Ophthalmol 1982;94:744-749.
16. Lightfoot D, Irvine AR. Am J Ophthalmol 1982;94:305-312.
17. Schepens CL. Am J Ophthalmol 1981;91:143-171.
18. Jabbour NM, Eller AE, Hirose T, Schepens CL, Liberfarb R, et al. Ophthalmology 1987;94:1640.

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Amyloidosis, Silicone Vitreoretinopathy, pg2

AMYLOIDOSIS

Vitreous amyloidosis is usually associated with primary familial amyloidosis. It is important to recognize vitreous amyloidosis because it may be the presenting sign or symptom of both systemic and ocular lesions, including proptosis, ocular palsies, internal ophthalmoplegia, neuroparalytic keratitis, glaucoma, and conjunctival involvement. [18, 19, 20, 21, 22, 23, 24]
Amyloidosis in the vitreous is causally linked with retinal blood vessel involvement. Vitreous amyloid may be dense enough to obscure vision or may be misinterpreted clinically as vitreous hemorrhage. [25] Biomicroscopically, the opacities may appear yellow-white and have a membranous veil-like quality (Figure 6-7). Some authors have described a central white dot associated with vertically oriented yellow strands. [26]
Vitrectomy may be done as a diagnostic or therapeutic maneuver. [27, 28, 29, 30] Intraocular washings reveal amorphous birefringent deposits that are enhanced with Congo red stain (Figure 6-8). Red-green dichroism may be observed in specimens stained with Congo red and illuminated with polarized light (Figure 6-9). Amyloid fluoresces with thioflavin T stain. It has been demonstrated that vitreous amyloid reacts immunocytochemically with antibody to prealbumin. [31] Familial amyloidosis of the neuropathic type has been associated with homozygosity for the transthyretin methionine-30 gene. [32]

SILICONE VITREORETINOPATHY

Silicone oil is used retinal detachment surgery as a means to tamponade retinal breaks and reattach the retina. [33, 34, 35] It is often reserved for cases of recurrent retinal detachments and advanced proliferative vitreoretinopathy. [36] There is experimental and clinical evidence to suggest that silicone oil may stimulate fibrous proliferation and recurrent membrane formation. [37, 38, 39, 40] Histologic studies have demonstrated glial or pigment epithelial tissue containing vacuoles as well as extracellular clear spaces. [41] Cytologic preparations show intracellular vacuoles that presumably represent silicone oil engulfed by glial cells and macrophages (Figure 6-10).

HEALON-LADEN MACROPHAGES

The differential diagnosis of clear vacuoles within macrophages includes residual healon (hyaluronic acid polymer). This viscoelastic substance is used mainly during cataract surgery to keep the ocular chambers formed so instruments glide smoothly through incisions and the corneal endothelium is protected from damage. Cytologic specimens show macrophages with cytoplasmic clear spaces (Figure 6-11). A proliferative reaction has not been reported with healon.

REFERENCES:
18. Lieberman TW, Ferry AP. Trans Am Ophthalmol Soc 1974;72:302-325
19. Kaufman HE. Arch Ophthalmol 1958;60:1036-2043
20. Crawford JB. Arch Ophthalmol 1967;78:214-216
21. Wong VG, McFarlin DE. Arch Opththalmol 1967;78:208-213
22. Legrand J. Guenel J, Dubigeon P. Bull Soc Ophtalmol Fr 1968;68:13-20
23. Hamburg A. Ophthalmologica 1971;162:173-177
24. Franceschetti AT, Rabinowicz T. J Genet Hum 1969;17:349-366
25. Schwartz MF, Green WR, Michels RG, Kincaid MC, Fogle J. Ophthalmology 1982;89:394-401
26. Mieler WF, Williams DF, Levin M. Arch Ophthalmol 1988;106:881-883
27. Paton D, Duke JR. AJO 1966;51:736-747
28. Kasner D, Miller GR, Taylor WH, Sever RJ, Norton EW, et al Trans Am Acad Ophthalmol Otolaryngol 1968;72:410-418
29. Matsui M, Tashiro T, Asai Y. Acta Soc Ophthalmol Jpn 1976;80:142-146
30. Irvine AR. Char DH. AJO 1976;82:705-708
31. Doft BH, Rubinow A, Cohen AS. AJO 1984;97:296-300
32. Sandgren O, Holmgrem G, Lundgren E. Arch Ophthalmol 1990;108:1584-1586
33. Cibis PA, Becker B, Okun E, Canaan S. Arch Ophthalmol 1962;68:590-599
34. Grey RHB, Leaver PK. BF J Ophthalmol 1979;92:1029-1034
35. McCuen BW II, Landers MB III, Machemer R. Ophthalmology 1985;92:1029-1034
36. Cox MS, Trese MT, Murphy PL. Ophthalmology 1986;93:646-650
37. Fastenberg DM, Diddie KR, Delmage JM, Dorey K. AJO 1983;95:663-667
38. Gonvers M, ThresherR. Graefes Arch Clin Exp Ophthalmol 1983;221:46-53
39. Watzke RC. Arch Ophthalmol 1967;77:185-196
40. Cockerham WD, Schepens CL, Freeman HM. Arch Ophthalmol 1970;83:704-712
41. Lewis H, Burke JM, Abrams GW, Aaberg TM. Ophthalmology 1988; 95:583-591

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CHAPTER 6 Vitreous Abnormalities page 1

CHAPTER 6 Abnormalities of the Vitreous Body

Most abnormalities of the vitreous body (vitreous) are too subtle to be diagnosed by intraocular washings alone. These subtle changes are diagnosed by careful biomicroscopic examination in the living patient or with the dissecting microscope in the enucleated specimen. However, there are a few important conditions, such as amyloid, silicone retinopathy, and asteroid hyalosis, that are evident by examination of extracted vitreous. Other conditions, such as persistent hyperplastic primary vitreous, are considered in the clinical diagnosis of malignant tumors in children and it is important to be aware of their existence. Vitreous hemorrhage and hemoglobin spherulosis are presented in Chapter 5.

PERSISTENT HYPERPLASTIC PRIMARY VITREOUS

Persistent hyperplastic primary vitreous (PHPV) is a congenital condition most commonly unilateral in which there is persistent hyaloid vasculature and mesenchymal tissue from the embryonic primary vitreous in a microphthalmic eye. [1, 2, 3] Fibrovascular tissue and mesenchymal tissue are attached laterally to elongated and centrally dislocated ciliary processes (Figure 6-1 and 6-2). The lens-iris diaphragm may be anteriorly displaced and produce secondary angle-closure glaucoma. Cartilage, mature adipose tissue, and smooth muscle may arise from primitive mesenchymal tissue behind the lens. [4, 5, 6] There is frequently an accompanying total exudative retinal detachment (Figure 6-1). Clinically, the patient usually has a white papillary reflex (leukocria), poor vision, and a small eye. PHPV can be confused with retinoblastoma, although existence of leukocoria at birth and microphthalmia is highly suggestive of PHPV. If retinoblastoma is a series consideration in the differential diagnosis or if surgical repair is considered for PHPV, preoperative fine needle aspiration or intraocular washing may be used. Smears show spindle cells and retinal tissue (Figure 6-3). Unlike retinoblastoma, the cells of PHPV are usually more cohesive and do not exhibit extensive necrosis.

ASTEROID HYALOSIS

Asteroid hyalosis is a disorder in which white-yellow smooth refractile spheres are suspended in the collagenous framework of the vitreous body. It is often unilateral, but can be bilateral. It is more common in older people. [7] The opacities are composed of complex lipids, calcium, and phosphorous. [8, 9, 10] Histochemically, the matrix of the opacities stain with periodic acid-Schiff, alcian blue, Sudan black B, and oil red O. [11] clinically asteroid hyalosis is often asymptomatic with good visual acuity. However, it may be very dense and it may obscure vision. [12, 13] In addition, the poor funduscopic view occasionally prevents adequate laser photocoagulation in patients with concomitant retinopathy (Figure 6-4). Vitrectomy may be indicated to improve vision or to improve the view of the fundus for the surgeon. [14] Cytologic specimens reveal amorphous round bodies that are birefringent in polarized light (Figures 6-5 and 6-6). There may be an associated foreign-body reaction. [10]
The cause of asteroid hyalosis is not known. Even though lipid is present in the yellow particles, there is no clear association with diabetes and hypercholesterolemia. [15, 16, 17]
References:
1. Reese AB. Arch Ophthalmol 1949;41:527-549.
2. Reese AB. AJO 1955;40:317-331.
3. Haddad R, Font, RL, Reeser F. Surv Ophthalmol 1978;23:123
4. Font RL, Yanoff M, Zimmerman LE. Arch Ophthalmol 1969;82:43-50
5. Manschot WA. Arch Ophthalmol 1958;59:188-203
6. Reese AB, Payne F. AJO 1964;29:1-19
7. Rutherford CW. Arch Ophthalmol 1933;9:106
8. Verhoeff FH. AJO 1921;4:155-160
9. March W, Shock D, O' Grady R. Invest Ophthalmol 1974;13:701705
10. Miller H, Miller B, Rabinowitz H, et al. Invest Ophthalmol Vis Sci 1983;24:133-136
11. Rodman HI, Johnson FB, Zimmerman LE. Arch Ophthalmol 1961;66:552-563
12. Engel HM, Green WR, Michels RG, Rice TA, Erozan YS, et al. Retina 1981;1:121-149
13. Renaldo DP. Retina 1981;1:252-254
14. Lambrou FH, Sternberg P, Meredith TA, Mines J, Fine SL. Ophthalmic Surg 1989;20:100-102
15. Smith JL. JAMA 1958;168:891-893
16. Hatfield RE, Gastineau CF, Rucker CW. Mayo Clin Proc 1962;37:513-514
17. Luxenberg MN, Sime D. AJO 1969;67:406-413

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Chapter-5-page4-References-CiliaryBody

14. Bonamour MM, Bonnet JC, Jambon M. Leiomyome du corps ciliaire; quelques considerations a propos du diagnostic et du traitement des tumeur benignes de l’iris et du corps ciliaire. Bull Soc Ophtalmol Fr 1957;7-8:482.
15. Calmettes L, Deodati F, Bec P. Leiomyome du corps ciliare. Bull Soc Ophtalmol Fr 1961;74:158-168.
16. Allen RA. Leiomyoma of ciliary body. Case presented at the Verhoeff Society, Washington, D.C., April 24-27, 1967.
17. Meyer SL, Fine BS, Front RL, Zimmerman LE. Leiomyoma of the ciliary body. Electron microscopic verification. Am J Ophthalmol 1968;66:1061-1068.
18. Calhoun FP Jr. Leiomyoma of the ciliary body. Case presented at the Verhoeff Society, Washington, D.C., April 26-29, 1976.
19. Jakobiec FA, Font RL, Tso MOM, Zimmerman LE. Mesectodermal leiomyoma of the ciliary body. A tumor of presumed neural crest origin. Cancer 1977;3 9:2102-2113.
20. Jakobiec FA, Iwamoto T. Mesectodermal leiomyoma of the ciliary body associated with a nevus. Arch Ophthalmol 1978;96:692-695.
21. Zimmerman LE. Melanocytes, melanocytic nevi, melanocytomas. Invest Ophthalmol 1965;4:11-40.
22. Reidy JJ, Apple DJ, Steinmetz RL, et al. Melanocytoma nomenclature, pathogensis, natural history and treatment. Surv Ophthalmol 1985;29:319-327.
23. Frangieh GT, El Baba F, Traboulsi El, et al. Melanocytoma of the ciliary body: presentation of four cases and review of nineteen reports. Surv Ophthalmol 1985;29:328-334.
24. Streeten BF, McGraw JL. Tumor of the ciliary pigment epithelium. Am J Ophthalmol 1972;74:420-429.
25. Wilensky JT, Holland MG. A pigmented tumor of the ciliary body. Arch Ophthalmol 1974;92:219-220.
26. Chang M, Shields JA, Wachtel DL. Adenoma of the pigment epithelium of the ciliary body simulating a malignant melanoma. Am J Ophthalmol 1979;88:40-44.
27. Anderson SR. Medulloepithelioma of the retina. In: Zimmerman LE, ed. Tumors of the eye and adnexa. Int Ophthalmol Clin 1962;2:483-506.
28. Leib WE, Shields JA, Eagle RC, Kwa D, Shields CL Cystic adenoma of the pigmented ciliary epithelium. Ophthalmol 1990;97:1489-1493.
29. Char DH, Miller TR, Crawford JB. Cytopathologic diagnosis of benign lesions simulating choroidal melanomas. Am J Ophthalmol 1991;112:70-75.
30. Jensen OA. Malignant melanoma of the human uvea. Acta Ophthalmol (Suppl.) 1963;75:17-215.
31. Raivio I. Uveal melanomas in Finland; an epidemiological, clinical, histological and prognostic study. Acta Ophthalmol (Suppl.) 1977;133:1-64.
32. Apt L. Uveal melanomas in children and adolescents. Int Ophthalmol Clin 1963;2:403-410.
33. Holland G. Clinical features and pathology of pigment tumours of the iris. Klin Monatsbl Augenheikd 1967;150:350-370.
34. Rones B, Zimmerman LE. The prognosis of primary tumors of the iris treated by iridectomy. Arch Ophthalmol 1958;60:193-205.
35. Shields JA, Sandborn GE, Augsburger JJ. The differential diagnosis of malignant melanoma of the iris. A clinical study of 200 patients. Ophthalmol 1983;90:716-720.
36. Callender GR. Malignant melanotic tumors of the eye. A study of histologic types in 111 cases. Trans Am Acad Ophthalmol Otolaryngol 1931;36:131.
37. Jakobiec FA, Silbert G. Are most iris “melanomas” really nevi? Arch Ophthalmol 1981;99:2117-2132.
38. Arentsen JJ, Green WR. Melanoma of the iris: report of 72 cases treated surgically. Ophthalmic Surg 1975;6:23-37.
39. Ashton N. Primary tumours of the iris. BR J Ophthalmol 1964;48:650-668.
40. Char DH, Crawford JB, Gonzales, Miller T. Iris melanoma with increased intraocular pressure. Differentiation of focal solitary tumors from diffuse or multiple tumors. Arch Ophthalmol 1989;107:548-551

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chapter-5-page3-Iris, Ciliary Body, Melanoma

IRIS AND CILIARY BODY MELANOMA

Melanomas in the eye most commonly occur in the choroids (see Chapter 9). However, about 3% to 16% (41% in children) of ocular melanomas arise in the iris and 9% to 10% arise in the ciliary body. [30, 31, 32, 33] Clinically, iris melanomas are highly vascular, pigmented lesions that usually occur inferiorly in the iris. [34, 35] The Callender classification of uveal melanomas as spindle or epithelioid does not apply to iris melanomas. [36, 37, 38] Iris melanomas have a much better prognosis than their ciliary body and choroidal counterparts. [39] Occasionally, malignant melanomas extend circumferentially about the ciliary body, yet clinically only a focus iris lesion is present (Figure 5-16). Determination of cell type in these cases may be helpful to document the presence of nucleoli suggesting a more atypical type of melanoma (Figure 5-17). Fine needle may be quite helpful in determining the presence of a ring melanoma of the ciliary body if the aspirate is performed away from the apparent lesion (Figure 5-18 and 5-19). Fine needle aspiration has been used to diagnosis iris masses and, specifically, to help determine if a pigmented lesion in the iris or ciliary body is focal, multiple, or diffuse. [40] However, on cytologic criteria alone, it is not possible to determine the original site of melanomas.

REFERENCE


30. Jensen OA. Malignant melanoma of the human uvea. Acta Ophthalmol (Suppl.) 1963;75:17-215.
31. Raivio I. Uveal melanomas in Finland; an epidemiological, clinical, histological and prognostic study. Acta Ophthalmol (Suppl.) 1977;133:1-64.
32. Apt L. Uveal melanomas in children and adolescents. Int Ophthalmol Clin 1963;2:403-410.
33. Holland G. Clinical features and pathology of pigment tumours of the iris. Klin Monatsbl Augenheikd 1967;150:350-370.
34. Rones B, Zimmerman LE. The prognosis of primary tumors of the iris treated by iridectomy. Arch Ophthalmol 1958;60:193-205.
35. Shields JA, Sanborn GE, Augsburger JJ. The differential diagnosis of malignant melanoma of the iris. A clinical study of 200 patients. Ophthalmol 1983;90:716-720.
36. Callender GR. Malignant melanotic tumors of the eye. A study of histologic types in 111 cases. Trans Am Acad Ophthalmol Otolaryngol 1931;36:131.
37. Jakobiec FA, Silbert G. Are most iris “melanomas” really nevi? Arch Ophthalmol 1981;99:2117-2132.
38. Arentsen JJ, Green WR. Melanoma of the iris: report of 72 cases treated surgically. Ophthalmic Surg 1975;6:23-37.
39. Ashton N. Primary tumours of the iris. BR J Ophthalmol 1964;48:650-668.
40. Char DH, Crawford JB, Gonzales, Miller T. Iris melanoma with increased intraocular pressure. Differentiation of focal solitary tumors from diffuse or multiple tumors. Arch Ophthalmol 1989;107:548-551

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Chapter-5-page2-Coronal Adenoma, Leiomyoma

CORONAL ADENOMA
The coronal adenoma, also called benign adenoma, Fuch’s adenoma, Fuch’s epithelioma, and epithelial hyperplasia, is the most common intraocular tumor. [6, 7] These adenomas originate from the nonpigmented epithelium of the pars plicata (the coronal processes) (Figure 5-6). They occur more commonly in older individuals. [8] Histologic sections show nonpigmented ciliary epithelium embedded in a matrix of basement membrane material (Figure 5-7). Rarely, these tumors are clinically misdiagnosed as melanoma because they indent the iris and mimic a pigmented lesion. [9, 10]Aspiration biopsy will distinguish melanoma from coronal adenoma. Fine needle aspiration of coronal adenomas has revealed cohesive groups of nonpigmented epithelium with bland nuclei and abundant cytoplasm clustered around extracellular matrix material (Figure 5-8). [11] Ultrastructural and immunohistochemical studies indicate that the extracellular matrix material contains Type IV collagen. [12]

LEIOMYOMA
Leiomyomas of the ciliary body are rare. [13, 14, 15, 16, 17, 18] They presumably arise from ciliary muscle. The clinical diagnosis may be suggested by augmented transillumination. Electron microscopic identification of myofilaments and micropinocytotic vesicles differentiates these tumors from neurofribromas and schwannomas.
Mesectododermal leiomyomas of the ciliary body are extremely rare. [19] Fine needle aspiration characteristics of these tumors have not been reported previously. We reviewed a fine needle aspiration of one such tumor from the UCLA cytology archives. The aspirate shows tight clusters of spindle and oval cells in a fibrillary background. The nuclei are extremely bland with inconspicuous nucleoli (Figure 5-9). Sections reveal an amelanotic ciliary body mass with prominent vascularity, a fibrillary and myxoid background, and individual tumor cells that are both spindled and oval shape (Figure 5-10 and 5-11). These findings suggest a neural tumor, yet electron microscopy shows smooth muscle differentiation. [20]

MELANOCYTOMA
Melanocytoma is a benign lesion found most commonly in blacks. [21, 22] It may be found in any part of the uveal tract, but is generally present adjacent to the optic disc. Melanocytomas occasionally occur in the ciliary body. [23] The cells of a melanocytoma are large with abundant densely pigmented cytoplasm and round nuclei with small nucleoli (Figure 5-12).

ADENOMA AND CARCINOMA OF THE PIGMENTED CILIARY EPITHELIUM
Adenomas of the pigmented ciliary epithelium may clinically mimic ciliary body melanomas because they are densely pigmented (Figure 5-13). [24, 25, 26] In general, they tend to be only locally invasive. [27] Immunohistochemical studies suggest that the tumor arises from the pigmented ciliary epithelium. [28] Histologically, the tumor replaces the ciliary body and is composed of large pigmented cells arranged in a nodular pattern (Figure 5-15). Cytologic findings include large cell with abundant intracellular and extracellular pigment, and round nuclei without prominent nucleoli. [29]

References:

6. Fuchs E. Anatomische miscellen. Albrecht Von Graefes Arch Klin Ophthalmol 1883;29:209.
7. Bateman JB, Foos RY. Coronal adenomas. Arch Ophthalmol 1979;97:2379-2384.
8. Iliff W, Green WL. The incidence and histology of Fuchs’ adenoma. Arch Ophthalmol 1972;88:249-254.
9. Burch PG, Maumenee AE. Iridocyclectomy for benign tumors of the ciliary body. Am J Ophthalmol 1967;63:447-452.
10. Zaidman GW, Johnson BL, Salamon SM, Mondino BJ. Fuch’s adenoma affecting the peripheral iris. Arch Ophthalmol 1983;101:771-773.
11. Glasgow BJ. Intraocular fine needle aspiration biopsy of coronal adenomas. Diagn Cytopathol 1991;7:239-242.
12. Brown HH, Glasgow BJ, Foos RY. Coronal adenomas: ultrastructural and immunohistochemical features. Am J Ophthalmol 1991;112:34-40.
13. Blodi FC. Leiomyoma of the ciliary body. Am J Ophthalmol 1950;33:939-942.
14. Bonamour MM, Bonnet JC, Jambon M. Leiomyome du corps ciliaire; quelques considerations a propos du diagnostic et du traitement des tumeur benignes de l’iris et du corps ciliaire. Bull Soc Ophtalmol Fr 1957;7-8:482.
15. Calmettes L, Deodati F, Bec P. Leiomyome du corps ciliare. Bull Soc Ophtalmol Fr 1961;74:158-168.
16. Allen RA. Leiomyoma of ciliary body. Case presented at the Verhoeff Society, Washington, D.C., April 24-27, 1967.
17. Meyer SL, Fine BS, Front RL, Zimmerman LE. Leiomyoma of the ciliary body. Electron microscopic verification. Am J Ophthalmol 1968;66:1061-1068.
18. Calhoun FP Jr. Leiomyoma of the ciliary body. Case presented at the Verhoeff Society, Washington, D.C., April 26-29, 1976.
19. Jakobiec FA, Font RL, Tso MOM, Zimmerman LE. Mesectodermal leiomyoma of the ciliary body. A tumor of presumed neural crest origin. Cancer 1977;3 9:2102-2113.
20. Jakobiec FA, Iwamoto T. Mesectodermal leiomyoma of the ciliary body associated with a nevus. Arch Ophthalmol 1978;96:692-695.
21. Zimmerman LE. Melanocytes, melanocytic nevi, melanocytomas. Invest Ophthalmol 1965;4:11-40.
22. Reidy JJ, Apple DJ, Steinmetz RL, et al. Melanocytoma nomenclature, pathogensis, natural history and treatment. Surv Ophthalmol 1985;29:319-327.
23. Frangieh GT, El Baba F, Traboulsi El, et al. Melanocytoma of the ciliary body: presentation of four cases and review of nineteen reports. Surv Ophthalmol 1985;29:328-334.
24. Streeten BW, McGraw JL. Tumor of the ciliary pigment epithelium. Am J Ophthalmol 1972;74:420-429.
25. Wilensky JT, Holland MG. A pigmented tumor of the ciliary body. Arch Ophthalmol 1974;92:219-220.
26. Chang M, Shields JA, Wachtel DL. Adenoma of the pigment epithelium of the ciliary body simulating a malignant melanoma. Am J Ophthalmol 1979;88:40-44.
27. Anderson SR. Medulloepithelioma of the retina. In: Zimmerman LE, ed. Tumors of the eye and adnexa. Int Ophthalmol Clin 1962;2:483-506.
28. Leib WE, Shields JA, Eagle RC, Kwa D, Shields CL Cystic adenoma of the pigmented ciliary epithelium. Ophthalmol 1990;97:1489-1493.
29. Char DH, Miller TR, Crawford JB. Cytopathologic diagnosis of benign lesions simulating choroidal melanomas. Am J Ophthalmol 1991;112:70-75.

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Chapter-5-page1-Abnormalities-Iris, Ciliary Body, Anterior-Chamber Angle

CHAPTER 5

Abnormalities of the Iris, Ciliary Body, and Angle Structures

In this chapter, lesions of the iris, ciliary body, and anterior chamber angle that are important in ocular cytology are illustrated. There are only a few lesions of the ciliary body, iris, and angle that are frequently ecountered in cytologic specimens. Infectious processes of the anterior chamber, iris, and ciliary body are presented in Chapter 8. Leukemias may involve the iris and shed cells into the aqueous, but are presented with other malignant neoplasms in Chapter 9. Choroidal melanomas are illustrated here.

HEMOGLOBIN SHERULOSIS AND GHOST ERYTHROCYTES

Red blood cells that have hemolyzed and hemoglobin aggregates can be identified on cytologic examination from vitrectomy and aqueous specimens [1]. Ghost erythrocytes are red blood cells in which the bulk of the hemoglobin has been extruded, leaving behind small fragments of hemoglobin festooned along the cell membrane remnants. Ghost erythrocytes are important to identify because they may enter the anterior chamber angle, obstruct the trabecular meshwork, and produce ghost-cell glaucoma [2]. Ghost-cell glaucoma has been reported after vitreous hemorrhage associated with cataract extraction or diabetic retinopathy [3].
Ghost cells appear on cytologic preparations as small ovoid to circular rings with central clear areas corresponding to the absence of hemoglobin. The hemoglobin is clumped at the periphery of the cell-forming Heinz bodies (Figure 5-1). Hemoglobin spherules are spheres of hemoglobin varying markedly in size, some of which are smaller than normal erythrocytes and others three to five times the diameter of red blood cell (Figure 5-2). Like ghost cells, hemoglobin spherules may obstruct the trabecular meshwork and produce glaucoma. If ghost cells or hemoglobin aggregates are diagnosed by cytologic examination of an aqueous, vitrectomy may be indicated in aphakic patients to relieve glaucoma [4].

PARS PLANITIS

Pars planitis is a condition in which cells and membranous veils are observed in the vitreous overlying the pars plana. This finding is termed “snowbanking.” [5] The cause of the disease is unknown. It is usually bilateral and occurs in young individuals. The collection of vitreous cells may obscure visions. Occasionally, vitrectomy may be done if an infectious agent is sought or if the opacity is chronic and severely limits vision. Histologically, lymphocytes and macrophages are seen adjacent to hyper-plastic non-pigmented ciliary epithelium. In the chronic condition, membranes may form over the pars plana composed of collagen and scare spindle cells (Figure 5-3). Perivascular sheathing of lymphocytes may also be seen (Figure 5-4). Cytologic preparations show lymphocytes and macrophages enmeshed in fibroglial membranous fragment (Figure 5-5). There finding are not specific, and the diagnosis requires careful clinical correlation.

References:
1. Grossniklaus HE, Frank KE, Farhi DC, Jacobs G, Green WR. Hemoglobin spherulosis in the vitreous cavity. Arch Ophthalmol 1988;106:961-962.
2. Campbell DG, Simmons RJ, Grant WM. Ghost cells as a cause of glaucoma. Am J Ophthalmol 1976;81:441-450.
3. Campbell DG, Essigmann EM. Hemolytic ghost cell glaucoma. Arch Ophthalmol 1979;97:2141-2146.
4. Brucker AJ, Michels RG, Green WR. Pars plana vitrectomy in the management of blood induced glaucoma with vitreous hemorrhage. Ann Ophthalmol 1978;10:1427-1437.
5. Pederson JE, Kenyon KR, Green WR, et al. Pathology of pars planitis. Am J Ophthalmol 1978;86:762-774.

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Chapter-4-page2

Chapter 4-page 2
PHACOANAPHYLACTOID AND PHACOLYTIC REACTIONS

Acute traumatic lens injury may result in a release of lens protein followed by a suppurative and granulomatous inflammatory response (Figure 4-11). Cytologically, the macrophages show ingested lens material (Figure 4-12) [12]. Macrophages may obstruct the trabecular meshwork and produce elevated intraocular pressure (phacoanaphylactic glaucoma) [13]. In hypermature cataracts, lens protein may leak through the capsule without evidence of trauma and produce a macrophage inflammatory response that may obstruct the trabecular meshwork (phacolytic glaucoma) [14]. In addition, soluble lens proteins can obstruct aqueous outflow pathways and may be a factor in both of these lens-related glaucomas [15].

REFERENCE

12. Goldberg MF. Cytological diagnosis of phacolytic glaucoma utilizing Millipore filtration of the aqueous. Br J Ophthalmol 1967;51:847.
13. Yanoff M, Scheie HG. Cytology of human lens aspirate. Arch Ophthalmol 1968;80:166-170.
14. Flocks M, Littwin CS, Zimmerman LE. Phacolytic glaucoma. Arch Ophthalmol 1955;54:37-45.
15. Epstein DL, Jedziniak JA, Grant MW. Obstruction of aqueous outflow by lens particles and by heavy molecular weight soluble lens protein. Invest Ophthalmol Vis Sci 1978;17:272-277.

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chapter-4-page1

CHAPTER 4

Abnormalities of the Lens

The human lens has a limited response to a wide range of noxious stimuli. The common final end point is cataract, a lenticular opacity produced by degenerative changes in crystalline proteins, Cataracts may form in different parts of the lens depending on the stimulus. Although often distinctive clinically, they are not distinguishable cytologically because the cataractous lens is emulsified by ultrasound (phacoemulsification) or chopped by a vitrectomy cutting instrument. In this chapter, those lens abnormalities that can be diagnosed by cytologic examination are illustrated.

CONGENITAL CATARACTS

There are many clinical types of congenital cataracts, including anterior polar, posterior polar zonular, sutural, membranous, and filiform. The clinical classification is based on location and slit lamp appearance. These types of cataracts cannot be distinguished in most cytologic preparations because they are generally removed by emulsifying the lens with a cutting instrument (e.g., ocutome). Despite the distortion in anatomic organization, numerous nuclei are often apparent in lens fibers of congenital cataracts obtained by emulsification (Figure 4-1) [1]. Rubella produces numerous changes in the eyes of infants, including retinopathy, nongranulomatous uveitis, glaucoma, and congenital cataract (Figure 4-2). Rubella-induced cataracts have been reported to show characteristic retention of nuclei in lens fibers (Figures 4-3 and 4-4) [2, 3, 4, 5, 6]. This feature can be seen in other types of congenital cataract [7, 8].

ADULT CATARACTS

Most adult cataracts have opacities in multiple locations within the lens. Commonly, they are opaque in both the centrally located nucleus (nuclear sclerosis or nuclear cataract)(Figure 4-5) and the peripherally located cortex (cortical cataract). Less often, opacities are present immediately beneath the capsule (subcapsular cataract). Some subcapsular cataracts are associated with trauma. Histologically, nuclear sclerotic cataracts show degenerative melding of lenticular fibers (Figure 4-6). Severely degenerated cortical lens fibers manifest as round eosinophilic globules (globular or Morgagnian degeneration). In cytologic preparations, Morgagnian globules can be identified (Figure 4-7). Sections of anterior and posterior subcapsular cataracts show a plaque of fibrous tissue and, presumably, lens epithelial cell proliferation immediately beneath the capsule (Figure 4-8) [9]. These cataracts are not usually sampled by extracapsular cataract extraction techniques.
Longstanding cataracts may become calcified [10] (cataracta calcarea) presumably by a dystrophic process [11]. In cytologic specimens, calcification appears as basophilic crystals, variable in size and shape, that exhibit birefringence (Figure 4-9 and 4-10). These crystals have been identified as calcium oxylate by x-ray diffraction and electron diffraction.


References:


1.Boniuk M. Rubella and other intraocular viral diseases in infancy. Int Ophthalmol Clin 1972;12:1-37.
2. Yanoff M, Schaffer DB, Scheie HG. Rubella ocular syndrome-clinical significance of viral and pathologic studies. Trans Am Acad Ophthalmol 1968;72:896-902.
3. Boniuk M, Zimmerman LE. Ocular pathology in the rubella syndrome. Arch Ophthalmol 1967;77:455-473.
4. Wolter JR, Insel PA, Willey EN, Brittain HP. Eye pathology following maternal rubella: a study of four children. J Pediat Ophthalmol 1966;3:29-35.
5. Zimmerman LE. The histopathologic basis for the ocular manifestations of the congenital rubella syndrome. Pro Inst Med Chicago 1968;26:170-192
6. Zimmerman LE, Font RL. Congenital malformations of the eye: some recent advances in knowledge of the pathogenesis and histopathological characteristics. JAMA 1966;196:684-692.
7. Hara J, Fujimoto F, Ishibashi T, Seguchi T, Nashimura K,et al. Ocular manifestations of the 1976 rubella epidemic in Japan. Am K Ophthalmol 1979;87:642-645.
8. Boger WP III. Late ocular complications in congenital rubella syndrome. Ophthalmology 1980;87:1244-1252.
9. Yanoff M, Fine BS. Ocular pathology, text and atlas. Philadelphia: J.B. Lippincott, 1989.
10. Harding CV, Chylack LT Jr., Susan SR, Lo W-K, Bobrowski WF, et al. Calcium containing opacities in the human lens. Invest Ophthalmol Vis Sci 1983;24:1194-1202.
11. Zimmerman LE, Johnson FB. Calcium oxalate crystals within ocular tissue. Arch Ophthalmol 1958;60:372-382.

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