IOVS, May 1999, Vol. 40, No. 6 Reports 1275 fore not clear whether the vascular regulation might be equally 3. Graham SL, Drance SM, Wijsman CJ, Mikelberg FS, Douglas GR. impaired in these two situations. This observation suggests that Ambulator)' blood pressure monitoring in glaucoma patients: the the possible vascular dysfunction underlying the glaucomatous nocturnal clip. Ophthalmology. 1995; 102:61-69. process is not tightly related to the stage of the disease. 4. Harris A, Sergott RC, Spaeth GL, et al. Color Doppler analysis of ocular vessel blood velocity in normal tension glaucoma. Am / Topicical dorzolamide reduced the IOP in our patients with Ophthalmol, 1994;118:642- 649. glaucoma (groups B and C). Our measurements showed that 5. Lieb WE, Cohen SM, Merton DA, ShieldsJA, Mitchell DC, Goldberg both, initial and advanced glaucomatous eyes, have lower IOPs BB. Color Doppler imaging of the eye and orbit: technique and (195 ± 3-6 and 19.6 ±31 mm Hg, respectively) after dorzol- normal vascular anatomy. Arch Ophtbalmol, 1991; 109:527-531. amide application than under baseline conditions (24.2 ± 5.3 and 6. Sergott RC, Aburn NS, Trible JR, Lieb WE, Falaharty PM. Color 24.1 ±4.1, respectively). Moreover, we have also observed that Doppler imaging: methodology and preliminary results in glau- the IOP increased in groups B and C after the initial dorzolamide coma. Sum Ophthalmol. l994;38(suppl):S65-S71. withdrawal. Our observation that dorzolamide reduces the IOP in 7. Williamson TH, Harris A. Color Doppler ultrasound imaging of the glaucomatous eyes and that it shows an additive effect with eye and orbit. Surv Ophthalmol. 1996;40:255-267. j3-blockers fully agrees with the observations reported in the 8. Kaiser HJ, Schoetzau A, Stiimpfig D, Flammer J. Blood flow veloc- 17 ities of the extraocular vessels in patients with high-tension and literature. On the other hand, in our study this hypotensive normal-tension primary open-angle glaucoma. Am J Ophthalmol. effect was not observed in healthy eyes. 1997;123:320-327. In summary, the main finding in the present study was that 9. Rankin SJA, Walman BE, Buckley AR, Drance SM. Color Doppler dorzolamide induces changes in ocular and periocular hemo- imaging and spectral analysis of the optic nerve vasculature in dynamics, improving blood perfusion of the eye. Improvement glaucoma. Am/ Ophthalmol, 1995;! 19:685-693- of blood flow, however, was not similar in all studied vessels. 10. Taylor KJW, Holland S. Doppler US, part 1: basic principles, instru- Hemodynamic changes in the OA were similar in normal and mentation and pitfalls. Radiology. 1990;l74:297-307. 11. Williamson TH, Baxter GM, Lowe GDO. The influence of age, glaucomatous eyes. In this vessel the PSV seems not to be systemic blood pressure, smoking and blood viscosity on orbital affected, whereas the EDV and the RI were improved. On the blood velocities. Br J Ophthalmol, 1995;79:17-22. contrary, dorzolamide induced different hemodynamic 12. Baxter GM, Williamson TH, McKillop G, Dutton GN. Color Dopp- changes in the CRA of normal and glaucomatous eyes. In this ler ultrasound of orbital and optic nerve blood flow: effects of vessel, the PSV increased in glaucomatous eyes but not in posture and timolol 0.5%. Invest Ophthalmol Vis Sci. 1992;33: normal eyes. The effect of the drug on the remaining hemody- 604-610. namic parameters of the CRA and CRV was similar in normal 13- Aim A, Bill A. The oxygen supply to the retina, II: effects of high and glaucomatous eyes. This differential effect of dorzolamide intraocular pressure and of increased arterial carbon dioxide ten- sion on uveal and retinal blood flow in cats—a study with labeled on the CRA of normal and glaucomatous eyes may be ex- microspheres including flow determinations in brain and some plained by the more prominent effect of the drug in lowering other tissues. Acta Physiol Scand. 1972;84:306-319. the IOP in the second group of eyes. 14. Harris A, Joos K, Kay M, Evans D, Shetty R, Sponsel WE. Acute IOP elevation with scleral suction: effects on retrobulbar haemodynam- Acknowledgments ics. Br J Ophthalmol. 1996;80:1055-1059- 15. Pillunat LE, Stodtmeister R, Wilmanns 1, Christ T. Autoregulation of The authors thank Jose Coclesido and Jose L. Otero for their help with ocular blood flow during changes in intraocular pressure, prelim- the color Doppler and the statistics. inary results. Graefes Arch Clin Exp Ophthalmol, 1985;223:219- References 223. 16. Harris A, Arend O, Arend S, Martin B. Effects of topical dorzol- 1. Drance SM. Glaucoma: a look beyond intraocular pressure. Am J amide on retinal and retrobulbar hemodynamics. Acta Ophthal- Ophtbalmol. 1997;123:817-819. mol Scand. 1996J 4:569-572. 2. Tielsch JM, KatzJ, Sommer A, Quigley HA, JavittJC. Hypertension, 17. Lippa EA. Carbonic anhydrase inhibitors. In: Rich R, Shields MB, perfusion pressure, and primary open-angle glaucoma: a popula- Krupin T, eds. TJie Glaucomas. New York: Mosby; 1996:1463- tion-based assessment. Arch Ophthalmol. 1995;113:2l6-221. 1481. Epitope Mapping of Anti- the characteristics, origin, and possible significance of these antibodies, the epitopic specificity of the anti-rho- Rhodopsin Antibodies from dopsin antibodies was examined in four NPG patients. Patients with Normal METHODS. Antibodies in patient sera were assayed by west- Pressure Glaucoma ern blot analysis against purified bovine rhoclopsin. Pep- tides derived from particular segments of the rhodopsin Carmelo Romano,l Zhengzhi Li,x sequence were tested for activity in competing for rho- Anatol Arendt,2 Paul A. Hargrave,2 and dopsin-antibody binding. Martin B. Wax1 RESULTS. Of a series of nine peptides that constitute most of the hydrophilic regions of rhodopsin, only one, consist- PURPOSE. The presence of anti-rhodopsin antibodies in ing of the C-terminal 25 amino acids, prevented binding of patients with normal pressure glaucoma (NPG) has been the patient antibodies to rhodopsin. Higher resolution previously demonstrated with western blot analysis and mapping using a set of dodecamers of overlapping se- enzyme-linked immunosorbent assay. To learn more about quences from the C-terminal region demonstrated that Downloaded from iovs.arvojournals.org on 10/01/2021 1276 Reports IOVS, May 1999, Vol. 40, No. 6 antibody binding is completely dependent on the last two Among the most interesting and perplexing associations amino acids. Removing the C-terminal alanine alone, or of glaucoma and autoimmunity are our previous findings that amidating the C terminus carboxyl group, also eliminated autoantibodies to rhodopsin are elevated in patients with nor- antibody binding. mal pressure compared with those with high pressure glau- coma or age-matched control patients.'' Glaucoma is tradition- CONCLUSIONS. Because four of four patient antibodies ex- ally considered to be a disease of ganglion cell layer loss, with amined exhibited the identical epitopic specificity, it is little or no subjective symptoms or signs that suggest photore- likely that a common mechanism underlies their genera- ceptor involvement. Therefore, although we considered the tion. This may indicate that molecular mimicry has oc- presence of elevated serum antibodies to rhodopsin a biochem- curred, because several pathogens contain similar C-ter- ical parameter indicating that the mechanism(s) of optic atro- minal sequences. Although they may serve as diagnostic phy in NPG and high pressure glaucoma may be distinctly markers, and provide evidence that there is an autoim- different, we were unable to conclude that elevated rhodopsin mune component in some patients with glaucoma, the antibodies were of pathogenic importance. To better under- role, if any, that these antibodies play in the pathogenesis stand the origin and potential significance of anti-rhodopsin of the disease remains unknown. (Invest Ophthalmol Vis antibodies in patients with NPG, we performed epitope map- Sci. 1999;40:1275-1280) ping to define in detail the immunogenic specificity of these antibodies. laucoma is no longer viewed simply as elevated intraocu- Glar pressure that damages the optic nerve. Studies have METHODS indicated that in a significant percentage of patients with glau- coma, intraocular pressure has never been demonstrated to be Patients elevated. The prevalence of this form of the disease, often All subjects were treated in accordance with the tenets of the called "normal pressure" or "low tension" glaucoma, is conser- Declaration of Helsinki. Blood samples were taken after de- vatively estimated to be approximately 20% to 30% of patients tailed consent was obtained from patients with NPG. Serum >2 with glaucoma.' Apoptotic cell death has been proposed to was prepared, heat inactivated, and stored at — 70°C until use. mediate the glaucomatous process in both high and normal The inclusion and exclusion criteria for these patients were pressure forms of experimental and human glaucoma.3"6 Al- described previously.1112 Briefly, NPG consisted of the pres- though neurodegenerative processes such as ischemia, excito- ence of open iridocorneal angles, no evidence of intraocular toxicity, neurotrophin insufficiency, and peroxynitrite damage pressure greater than 23 mm Hg, glaucomatous changes in have all been hypothesized to play a role in causing apoptotic visual fields and optic nerve cupping, and the absence of glaucomatous ganglion cell loss, none of these mechanisms alternative causes of optic neuropathy. Visual field loss of have been definitively linked to either the high or normal patients was evaluated with the Humphrey Field Analyzer, 30-2 pressure form of the disease. program (Humphrey Instruments, San Leandro, CA). Our cri- We have proposed that one form of normal pressure teria for visual field abnormalities included a corrected pattern glaucoma (NPG) may represent an autoimmune neuropathy. SD with a P < 0.05 or a glaucoma hemifield test outside normal Evidence that supports this includes immunoglobulin deposi- limits obtained with at least two reliable and reproducible tion in the ganglion cell layer observed in the postmortem visual field examinations.