by community ophthalmologists. We thank Dr. Garg forhis comments in an effort to further refine the role ofcorneal biopsy in the management of keratitis.

GEORGE ALEXANDRAKIS, MD

EDUARDO C. ALFONSO, MD

Miami, Florida

Open-angle Glaucoma AssociatedWith Graves Disease

EDITOR:

I READ WITH INTEREST THE ARTICLE BY OHTSUKA AND

Nakamura (Am J Ophthalmol 129:613–617, 2000). Theauthors concluded, “The prevalence of normal-tensionglaucoma as well as open-angle glaucoma and ocularhypertension was significantly higher among patients withGraves [sic] disease than in the general population.” Thedata provided by the authors appear to be insufficient tosupport such a conclusion.

The authors diagnosed glaucoma if a visual field defectwas associated with rim notching in the absence ofcomputed tomography evidence of enlarged muscles com-pressing the optic nerve at the orbital apex. The authorsdivided their group of glaucoma patients into two groups:those with an intraocular pressure below 21 mm Hg(normal-tension glaucoma) and those above 21 mm Hg(open-angle glaucoma). In addition, any patient with anintraocular pressure greater than 21 but without visual fieldloss was defined as an ocular hypertensive. I feel thisdefinition is inadequate to accurately diagnose glaucomawithin the dysthyroid ophthalmology patient population.

Ocular hypertension is very difficult to determine in thedysthyroid patient. It has been well established that in-traocular pressure may vary greatly, depending on theposition of the globe when the pressure is measured.1,2 Theauthors do not describe how they measured intraocularpressure. Dysthyroid changes in the orbit most commonlyinvolve the inferior rectus muscle. Intraocular pressuretypically increases as the eye is supraducted. If applanationtonometry is used at the slit lamp, this requires the eye tobe held in primary or slight upgaze, thus increasing theintraocular pressure. Further description of how the in-traocular pressures were obtained would be crucial to thediagnosis of glaucoma and ocular hypertension.

Dysthyroid optic neuropathy can occur in the absence ofdirect compression of the optic nerve at the orbital apex.3

Various mechanisms have been suggested, includingstretch of the optic nerve. Therefore, a portion of thepatients with visual field loss may be attributed to glau-coma, but in fact it may be attributed to dysthyroidorbitopathy.

I agree with the authors that glaucoma exists within thedysthyroid patient population. However, the data pre-sented appear inadequate to conclude that the prevalence

of glaucoma and ocular hypertension is greater in theGraves’ disease population than in the general population.The risk to such an assumption is that patients will beincorrectly diagnosed with glaucoma and appropriate man-agement for dysthyroid optic neuropathy delayed.

JAMES C. ORCUTT, MD, PHD

Seattle, Washington

REFERENCES

1. Gamblin G, Harper D, Galantine P, Buck DR, Chernow B, EilC. Prevalence of increased intraocular pressure in Graves’disease—evidence of frequent subclinical ophthalmopathy.N Engl J Med 1983;308:420–424.

2. Munoz M, Capo H. Differential intraocular pressure in restric-tive strabismus. Am J Ophthalmol 1991;112:352–353.

3. Anderson RL, Tweeten JP, Patrinely JR, Garland PE, ThieseSM. Dysthyroid optic neuropathy without extraocular muscleinvolvement. Ophthalmic Surg 1989;20:568–574.

AUTHOR REPLY

RESULTS OF SOME PREVIOUS STUDIES INDICATE THAT THE

increase in the volume of the retrobulbar tissue causesretrobulbar pressure to increase in patients with Graves’ophthalmopathy.1,2 We also indicated that the meanintraocular pressure was significantly higher in eyes withsevere proptosis than in nonproptotic eyes, and intraocularpressures were reduced significantly after orbital decom-pression in 95 patients with Graves’ ophthalmopathy.3

These findings suggest that increased intraorbital pressurewith proptosis leads to sustained ocular hypertension in allpositions of gaze, although a substantial increase in in-traocular pressure may occur in upward gaze because offibrosis of the inferior rectus muscle. Intraocular pressureshould be measured in primary gaze, slight downgaze andslight upgaze. If intraocular pressure is high in all positionsof gaze, ocular hypertension will be diagnosed.

In the present study, all patients were examined every 2months for a minimum of 2 years, and open-angle glau-coma was diagnosed in 14 patients. The visual fields ofthese patients were stable with glaucoma therapies withinthe follow-up period. Therefore, dysthyroid optic neurop-athy was able to be ruled out in these patients. As Dr.Orcutt stated above, it is not easy to clarify the cause ofvisual field defects in patients with Graves’ ophthalmopa-thy. We need follow-up examinations, when visual fielddefects are revealed in patients with Graves’ ophthalmop-athy.

KENJI OHTSUKA, MD, PHD

YASUSHI NAKAMURA, MD, PHD

Sapporo, Japan

AMERICAN JOURNAL OF OPHTHALMOLOGY292 FEBRUARY 2002

REFERENCES

1. Otto AJ, Spekreije H. Intraorbital volume discrepancies andintraorbital pressure. Int Ophthalmol 1987;11:113–114.

2. Otto AJ, Spekreije H. Volume discrepancies in the orbit andthe effect on intraorbital pressure. Orbit 1989;8:233–244.

3. Ohtsuka K. Intraocular pressure and proptosis in 95 patientswith Graves ophthalmopathy. Am J Ophthalmol 1997;124:570–572.

Ocular Features AssociatedWith Anticardiolipin Antibodies:A Descriptive Study

EDITOR:

IN THEIR REPORT “OCULAR FEATURES ASSOCIATED WITH

anticardiolipin antibodies: a descriptive study,” Miserocchiand colleagues describe a range of ocular findings among 13patients who were seen over a period of approximately 13years at the Massachusetts Eye and Ear Infirmary and whowere noted to produce anticardiolipin antibodies (Am JOphthalmol 131:451–456, 2001). This report is a poten-tial landmark study because it comes from an eminentgroup and it expands the spectrum of disease associatedwith anticardiolipin antibodies. Based on their data, theauthors “do not conclude that there is a causative role ofanticardiolipin antibodies in some patients with uveitis.”However, they advise that “one might want to includeanticardiolipin antibody screening in all patients present-ing with uveitis of unclear cause in which retinal vasculitisis involved.”1 We disagree with these statements. Toevaluate the conclusions of this report, it is important torecognize specifics about the anticardiolipin antibody andgeneral principles about laboratory testing.

Numerous studies have reported an association betweenocclusive retinal vascular disease, often associated withsome degree of intraocular inflammation, and antiphos-pholipid antibodies, including the anticardiolipin anti-body.2 Like other autoantibodies, anticardiolipin antibodiesmay be expressed at low levels by healthy individuals.Anticardiolipin antibodies are more commonly detected inpatients with specific inflammatory diseases, such as sys-temic lupus erythematosus, rheumatoid arthritis and auto-immune thyroiditis, certain infections including syphilis,and the primary antiphospholipid antibody syndrome.When present in clinically significant titers, the antibodiesare believed to have a causative role in vascular occlusiveepisodes and pregnancy losses.

To evaluate whether the presence of anticardiolipinantibody was clinically significant in the patients reportedby Miserocchi and coworkers, one needs to know thefollowing information:

1. Were measurements of the anticardiolipin antibodytiters performed more than once for each patient?

High interlaboratory variation in titer levels and ageneral lack of test result consensus between labora-tories are substantial concerns in the interpretationof anticardiolipin antibody assays.3 Measurement ofincreased levels of anticardiolipin antibody on two ormore occasions, at least 6 weeks apart, is consideredto be clinically significant.3

2. What were considered normal and increased anticar-diolipin antibody titers in the authors’ laboratory?The degree of increase is usually critical in evaluatingthe clinical implication of this antibody. Currentguidelines suggest that medium or high titers ofanticardiolipin IgM and IgG have clinical signifi-cance, whereas low titers of IgM and IgG, or an IgAof any titer do not.3

3. How often was the anticardiolipin antibody titernegative in a control population? Because as many as9.1% of otherwise healthy individuals may have apositive test for the antibody,4 did the frequency ofpositive tests exceed expectation?

The Bayes theorem provides a mathematical frameworkto evaluate the value of a laboratory test based on the test’ssensitivity and specificity, as well as the pretest likelihoodthat the patient has the suspected condition. We havepreviously utilized the Bayes theorem to demonstrate thatroutine screening tests such as antinuclear antibody andpurified protein derivative testing should not be indiscrim-inately ordered for all patients with uveitis.5 We agree withthe conclusions of another prominent group6 that labora-tory testing should be selectively ordered for patients withprimary retinal vasculitis.

The ultimate value of a laboratory test is its therapeuticimplication. Patients with clinically significant anticardio-lipin antibody titers are generally treated with high-intensity oral anticoagulation, a therapy that has potentialrisk. Rather than screening all patients with retinal vascu-litis of uncertain cause for the presence of anticardiolipinantibodies, we recommend this test for patients youngerthan age 45 who have suffered retinal vascular thrombosisand for patients with retinal vasculitis occurring in associ-ation with a collagen-vascular disease or a history ofvascular thrombosis or pregnancy loss.

JAMES T. ROSENBAUM, MD

JUSTINE R. SMITH, MBBS, PHD

Portland, Oregon

REFERENCES

1. Giorgi D, David V, Afeltra A, Gabrieli CB. Transient visualsymptoms in systemic lupus erythematosus and antiphospho-lipid syndrome. Ocul Immunol Inflamm 2001;9:49–57.

2. Favaloro EJ, Silvestrini R, Mohammed A. Clinical utility ofanticardiolipin antibody assays: high inter-laboratory varia-tion and limited consensus by participants of external quality

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