CASE PRESENTATIONS
The First Patient
A 49-year-old black male presents with a significant family history of blindness due to glaucoma; he reports that his uncle was blind prior to dying and that his aunt is currently being treated with glaucoma medications. I had first seen the patient 7 years earlier, at which time he was undergoing treatment with timolol. According to his history, his IOP had measured in the mid-20s prior to treatment. I stopped his medication and have followed the patient for the subsequent period of time.
At the current ocular examination, the patient's visual acuity is 20/15 OU, his IOP measurements without medication are 18 mm Hg OD and 20 mm Hg OS, and his pachymetry measurements are 617 µm OD and 601 µm OS (Figures 1 and 2). Should his medical therapy recommence?
Figure 1. The most recent chromatic visual fields of the first patient are shown.
Figure 2. The most recent nerve fiber analyses of the first patient are shown.
The Second Patient
The son of the glaucoma suspect described earlier presents with visual acuities of 20/20-2 OD and 20/20 OS, IOP measurements of 15 mm Hg OD and 16 mm Hg OS, and pachymetry measurements of 549 µm OD and 537 µm OS (Figures 3 and 4). His earlier treatment with a topical beta-blocker had been discontinued. Should this patient restart medical therapy?
Figure 3. The most recent chromatic visual fields of the second patient are shown.
Figure 4. The most recent nerve fiber analyses of the second patient are shown.
DR. MILLER'S RESPONSE
The Basis for Decision-Making
The choice to initiate treatment in a glaucoma suspect depends upon both the patient's baseline status and his risk factors for developing glaucoma. By definition, a glaucoma suspect must have at least one of the following: (1) optic disc cupping and/or nerve fiber layer loss suggestive of glaucoma, (2) possible early visual field loss, and/or (3) an IOP of greater than 22 mm Hg. When interpreting this information, clinicians take into account a patient's risk factors for glaucomatous development. The most significant factors include an IOP of greater than 22 mm Hg, African descent, thinner central corneas, an increased pattern of standard deviation on an otherwise normal Humphrey visual field (Carl Zeiss Meditec Inc., Dublin, CA), advanced age, and a family history of glaucoma.1
The decision to treat a glaucoma suspect is straightforward if his IOP is chronically elevated or undergoes wide diurnal fluctuation, especially if the patient's central corneal thickness is also in the normal-to-thin range. If the pressure is normal, I look for evidence of structural or functional damage before initiating treatment, even if multiple risk factors are present.
Patients are often classified as glaucoma suspects based on suspicious-looking optic discs, and the challenge when making a diagnosis is to distinguish physiologic cupping or a disc anomaly from glaucomatous cupping. Baseline documentation of the disc's appearance is therefore essential. Stereodisc photography is a time-honored method of documentation, and it is invaluable to discerning change over years of follow-up. This technique does not help distinguish normal from abnormal optic discs at baseline, however. New technologies that analyze optic disc topography and nerve fiber layer thickness are helpful in this regard. In the cases presented here, Dr. Higginbotham used scanning laser polarimetry to assess nerve fiber layer thickness. Patients with pathologic thinning of the disc rim should have corresponding nerve fiber layer loss. For that reason, the presence of a suspicious optic disc and a normal nerve fiber layer thickness suggests physiologic cupping, whereas the presence of local or diffuse nerve fiber layer loss confirms early glaucomatous damage.
When looking for evidence of early visual field loss, standard threshold automated perimetry such as the Humphrey 24-2 may be inadequate because at least 30% of the nerve is damaged before that destruction becomes manifest as a visual field defect. Short-wave automated perimetry (SWAP) (Carl Zeiss Meditec Inc.) can help clinicians detect early field loss because it tests a smaller subpopulation of ganglion cells and may reveal abnormalities 3 to 5 years before standard threshold automated perimetry would yield such findings. As a result, SWAP in a reliable patient that showed a defect corresponding to a suspicious disc finding would support treatment, while normal SWAP would make me more comfortable about following the patient without therapy.
The First Patient
The individual in question has several risk factors for glaucoma: race, a history of ocular hypertension, and a strong family history of glaucoma. In addition, he has suspicious optic disc cupping. It is unstated whether his brief treatment with timolol for ocular hypertension was stopped due to side effects or because his physician thought it safe to follow him without therapy. At his most recent examination, the patient's IOP was normal; more importantly, the central corneal thickness was increased, and, therefore, Goldmann applanation tonometry (617 µm OD, 601 µm OS) overestimated his true IOP.
SWAP, performed with good testing parameters, was normal. In addition, scanning laser polarimetry of the peripapillary nerve fiber layer showed a normal nerve fiber layer thickness, even though the cup-to-disc ratio was approximately 0.7. It would be useful to obtain a diurnal tension curve in order to check for an IOP spike, but the combination of at least a 7-year history as a glaucoma suspect, increased central corneal thickness, normal SWAP, and a normal nerve fiber layer indicates that the optic nerve cupping has likely not progressed. I therefore would not restart treatment at this time, but I would follow this patient at least every 6 months and repeat the SWAP and nerve fiber layer analysis on an annual basis in order to look for any evidence of change.
The Second Patient
The patient presents with a similar optic disc appearance and the same risk factors as his father's, except that this glaucoma suspect has no history of ocular hypertension. On examination, his IOP is in the mid-teens, and the central corneal thickness is normal. SWAP does not show any focal defects on the pattern deviation plot. The mean deviation is moderately increased in both eyes, but the total deviation plot is normal in the right eye and only slightly depressed inferiorly in the left. I was concerned that these parameters might indicate very early diffuse glaucomatous loss, but scanning laser polarimetry indicates a normal nerve fiber layer thickness bilaterally.
The patient briefly received treatment with timolol in the past, presumably based on the appearance of his optic disc. Again, the reason timolol was discontinued was not indicated, but a young male might be unlikely to remain compliant with treatment due to the potential beta-blocker–related side effects of decreased exercise tolerance and impotence. Based on the available information, I would not restart treatment but see him for a follow-up visit every 6 months to check for any evidence of an elevation in IOP, change in disc appearance, or visual field loss. I would repeat SWAP in 6 months, because I am concerned about the mean deviation, and I would repeat the nerve fiber layer analysis in 1 year.
The importance of the son's normal central corneal thickness is that, if ocular hypertension develops, the reading is a true indication of the pressure against the optic nerve head, whereas, in his father, the measurement is an overestimation. If the son develops ocular hypertension, he will be in the high anatomic risk category found in the Ocular Hypertension Treatment Study2,3 for converting to manifest glaucoma; he has a central corneal thickness of less than 556 µm and a vertical/horizontal cup-to-disc ratio of greater than 0.4. Combined with his other risk factors, that categorization would warrant initiating treatment.
At that point, I would start with a prostaglandin analogue because, as a group, these agents are more efficacious than beta-blockers and have fewer systemic side effects. If necessary, I would increase medical therapy in a stepwise fashion in order to achieve at least a 20% pressure reduction from baseline or an IOP of less than 20 mm Hg. If medical therapy proved ineffective or poorly tolerated, laser trabeculoplasty would be the next treatment option.
DR. HIGGINBOTHAM COMMENTS
Dr. Miller's decision simply to follow these two patients coincides with my own clinical plan. The absence of field defects on SWAP in both patients fairly satisfied me that neither individual has any functional abnormalities at this point. Nevertheless, there is always the strong possibility that structural findings may occur prior to the visual field finding. Because both patients understand their circumstances and due to the potential risks of not treating glaucomatous disease in these individuals given their family history, I continue to see both patients for a follow-up examination at least once a year.
Another point worth mentioning is the difference in corneal thickness within the same African American family. Although the Ocular Hypertension Treatment Study demonstrated that African Americans on average possess thinner corneas as compared with individuals of other races,2 clinicians cannot assume that all patients within a given ethnic background will follow the same trend in measurements. Actually, in light of the recent evidence from genetic studies4 regarding the similarities of populations across the world, the appropriateness of race as a way of classifying individuals is currently in question. As noted in a recent editorial in the New England Journal of Medicine,4 “race is a social construct, not a scientific classification.” It is therefore necessary to check the corneal thickness of all patients with ocular hypertension, rather than assume the outcome of any particular measurement. Mapping out an individualized treatment plan based on the patient's family history, age, and specific ocular risk factors such as cup-to-disc ratio and central corneal thickness is important. In these two cases, the treatment plan is observation.
Eve J. Higginbotham, MD, is Professor and Chair of the Department of Ophthalmology at the University of Maryland School of Medicine in Baltimore. Dr. Higginbotham was Vice Chair of the Ocular Hypertension Treatment Study and received NEI funds for its completion. She is a speaker for and has received grants from Pharmacia Corporation and Allergan, Inc. Dr. Higginbotham may be reached at (410) 328-5929; fcwejh6786@aol.com.
Eydie G. Miller, MD, is Clinical Associate Professor at the Scheie Eye Institute, University of Pennsylvania Health System. She holds no financial interest in the products mentioned herein. Dr. Miller may be reached at (215) 662-8188; eydie.miller@uphs.upenn.edu.
1. American Academy of Ophthalmology. Primary Open Angle Glaucoma Suspect, Preferred Practice Pattern. San Francisco: American Academy of Ophthalmology, 2002.
2. Brandt JD, Beiser JA, Klass MA, et al. Central corneal thickness in the Ocular Hypertension Treatment Study. Ophthalmology. 2001;108:1779-1788.
3. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: Baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714-720.
4. Schwartz, RS. Racial Profiling in Medical Research. N Engl J Med. 2001;344:18:1392-1393.
