Rate and Amount of Visual Loss in 102 Patients with Open-Angle Glaucoma Followed Up for at Least 15 Years

Transcription

1 Rate and Amount of Visual Loss in 102 Patients with Open-Angle Glaucoma Followed Up for at Least 15 Years Tarek M. Eid, MD, 1 George L. Spaeth, MD, 2 Anya Bitterman, MD, 3 William C. Steinmann, MD, MSc 2 Purpose: To determine the probability of worsening of glaucoma and the rate of change in patients having open-angle glaucoma for approximately 20 years. Design: Retrospective, noncomparative case series. Participants: One hundred and two patients diagnosed and treated for open-angle glaucoma before Testing/Intervention: The optic disc and visual field of one eye of each patient were graded independently at diagnosis and periodically throughout the follow-up period for a minimum of 15 years (mean, 19 3 years), using a scale ranging from 0 no damage to 5 far-advanced damage. Therapy was contemperaneous and stepped through medical laser, and surgery. Main Outcome Measures: The probability of worsening by one or more stages was plotted against the length of follow-up (Kaplan-Meier survival curves). Results: Nineteen eyes did not worsen, 43 deteriorated one stage, 31 two stages, and 9 three stages. The median time to first worsening was 7.5 years, to second worsening 18.5 years, and to third worsening 24.5 years. Patients with more advanced stages of damage were not more likely to deteriorate than those with less-marked damage. The intraocular pressure was not significantly lower in the patients who remained stable. Seventeen eyes deteriorated to a visual acuity of 20/200 or worse. Of these, causes other than glaucoma were responsible in at least 60% of the cases. Conclusions: Approximately 20% of eyes with open-angle glaucoma remained stable for about 20 years, 43% deteriorated one of five stages, and 9% three of five stages. Seventeen of the eyes lost acuity to a level of 20/200, usually from causes other than glaucoma. Deterioration of field was, on average, first noted at 7.5 years, after which the rate of deterioration slowed. Ophthalmology 2003;110: by the American Academy of Ophthalmology. Appropriate treatment of glaucoma requires an evaluation of the rate of deterioration of the disease over time. Most treatment outcomes reported for glaucoma reflect only a short-term follow-up. Without some sense of the rate of deterioration of the disease over time it is impossible to determine whether there is any benefit from treatment. Little information exists about the course of untreated glaucoma, and it is not likely, because of ethical and practical reasons, that such information will be developed. Therefore, we must Originally received: January 18, Accepted: August 22, Manuscript no Ophthalmology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. 2 William and Anna Goldberg Glaucoma Service, Wills Eye Hospital/ Jefferson Medical College, Philadelphia, Pennsylvania. 3 Wills Eye Hospital/Jefferson Medical College, Philadelphia, Pennsylvania. Supported in part by the Glaucoma Service Foundation to Prevent Blindness, Philadelphia, Pennsylvania. None of the authors has any proprietary interest in the development or marketing of any of the devices mentioned in this study. Reprint requests to George L. Spaeth, MD, William and Anna Goldberg Glaucoma Service, Wills Eye Hospital, 840 Walnut St., Philadelphia, PA rely on studies that characterize the course of treated glaucoma, which is important, because the aggressiveness of treatment should be based on the likely outcome of treatment. However, there is also relatively little information in this regard. Such information as does exist is mostly concerned with deterioration of the visual field We sought to provide data on the course of treated glaucoma over a prolonged time, assessing both the optic disc and the visual field evaluation. We reviewed the records of a group of patients with glaucoma who had been diagnosed, treated, and followed for a minimum of 15 years. The objectives of the study were (1) to determine the incidence of deterioration of the optic disc or visual field, (2) to determine the rate of worsening of the optic disc and visual field, and (3) to explore the relationship between deterioration of glaucoma and intraocular pressure. Patients and Methods All the medical records of patients who had been initially examined before 1982 and were still being followed by the senior author at Wills Eye Hospital were reviewed. Only patients continuously followed for at least 15 years were included. Patients needed to have had yearly evaluations, including assessments of the optic by the American Academy of Ophthalmology ISSN /03/$ see front matter Published by Elsevier Science Inc. doi: /s (03)

2 Eid et al Long-term Follow-up of Open-angle Glaucomas disc and visual field. Only patients with primary open-angle glaucoma (POAG), low-tension glaucoma (LTG), pigmentary glaucoma (PG), and glaucoma with the exfoliation syndrome (XFG) were eligible. For purposes of the study, open-angle glaucoma (POAG, PG, XFG) was defined as the presence of an intraocular pressure (IOP) greater than 21 mmhg; a normal, open anterior chamber angle; glaucomatous optic disc damage; and glaucomatous visual field defects. LTG was defined as the presence of optic disc and visual field changes characteristic of glaucomatous damage, with an IOP consistently less than 22mm Hg. An optic disc was considered glaucomatous if it had signs of focal or diffuse damage (a notch of the neuroretinal rim, acquired pit, 18 or documented narrowing of the neuroretinal rim). A visual field was regarded as glaucomatous if it had any of the following defects in the absence of nonglaucomatous lesions of the retina and choroid and of the optic disc, optic nerve, optic chiasm, or central visual pathways: a paracentral scotoma, a nasal step, an arcuate or annular scotoma, or an altitudinal scotoma. PG and XFG were considered present when the eyes showed the classic findings of these well-described entities. Patients who were seen only in consultation and returned to their primary physician were not included. The charts were originally screened by the first author (TME), and appropriateness for inclusion on the basis of preceding the criteria was confirmed by the senior author (GLS). Patients with grade V visual fields or grade V optic discs were excluded (the grading system is described in the following). One eye per patient was selected for study. In bilateral glaucoma, the eye with the earlier-onset disease at the time of initial examination was chosen. If this difference was not clear, the eye with more advanced disease when first seen was selected. All patients meeting the eligibility criteria were included, whether they had had filtering surgery or not. Data Collection Data abstracted from the record of each eligible patient included demographic variables (age, gender, and race), historical variables (family history of glaucoma, positive medical history of diabetes, hypertension, ischemic heart diseases, migraine, etc.; nonglaucomatous ocular diagnoses affecting visual acuity or visual field and previous and current antiglaucoma treatment); baseline ocular variables of the study eye (glaucoma diagnosis, IOP [Goldmann applanation tonometry], visual acuity [Snellen s chart], gonioscopic angle grading [Spaeth grading system], lens status [slitlamp evaluation], optic nerve head appearance [fundus photography and disc drawing], and visual field features [Goldmann perimeter and Octopus and Humphrey perimeters]). The optic disc changes were graded as follows: grade 0 rim tissue present in all quadrants without clinically detectable signs of glaucomatous damage; grade I rim present in all quadrants with (1) early signs of glaucomatous damage (focal notching, acquired pit of the optic nerve) either superiorly or inferiorly or (2) diffuse damage with a cup-to-disc ratio 0.7; grade II (1) no rim in less than one quadrant, (2) superior and inferior glaucomatous damage without total loss of rim tissue in either quadrant, or (3) diffuse concentric cupping with a cup-to-disc ratio 0.9; grade III (1) no rim in more than one and less than two quadrants, or (2) diffuse narrowing of the neuroretinal rim in all quadrants without total loss of rim in any quadrant (advanced concentric cupping [cup-to-disc ratio 0.9]); grade IV no rim in more than two and less than three quadrants; and grade V loss of rim in more than three quadrants. 19 The optic disc was evaluated and graded by a masked observer (TME) at each visit; when available, disc photographs were used. When disc photographs were not available at every periodic follow-up visit, disc drawings by the senior investigator were used for grading. Because of the diversity of the methods of visual field examinations (Goldmann, Humphrey, and Octopus perimetry) over the extended follow-up period, a generic grading system was used to grade the glaucomatous field defects: grade 0 no visual field defect present; grade I nasal step or localized paracentral defect; grade II nasal step and paracentral defect or a single arcuate defect; grade III two arcuate scotomas or an altitudinal scotoma not encroaching on fixation; grade IV advanced visual field loss abutting, but not involving, fixation; and grade V advanced visual field loss with loss of fixation. 19 The disc and field grading were performed by one examiner (TME) after a pilot study using the grading systems demonstrated a high rate of intraobserver reproducibility. This pilot study was performed before the major study reported here and was conducted as follows: Reproducibility of the disc grading system The photographs of the optic disc of 100 patients with varying degrees of glaucoma were independently graded by two authors (TME and GLS) masked to other information. In 86 cases there was complete agreement between the two graders, in 12 cases the graders differed by one stage, and in 2 cases the graders differed by two stages. In no case was there a difference of grading of more than two stages. Reproducibility of the visual field grading system (Goldmann, Octopus, and Humphrey) The results of visual field examinations of 100 patients with varying degrees of field loss were independently graded by two authors (TME and AB) masked to other information. In 87 cases both observers agreed, in 9 cases the observers differed by one stage, and in 4 cases the observers differed by two stages. In no case was there a difference of more than two stages. Reproducibility, then, for both the disc and the field grading systems was high. The agreement between the grade of the optic disc and the grade of the visual field showed a kappa of 0.59 and a Spearman correlation coefficient of r 8.55, indicating a strong association between the two variables. In this study the systems adopted for staging the glaucoma included considering the optic disc grade and the visual field grade separately, and, in addition, considering both the disc and field grade together. The selected stage used was the greater of the optic disc or visual field score. Thus, for example, stage 0 in this latter system meant that there was no glaucomatous damage by either disc or field evaluation, whereas stage V denoted almost total loss of the rim tissue in the optic disc or advanced visual field loss with loss of fixation, or both. Patients with stage V glaucomatous damage at the time of initial examination were not included in the study, because further deterioration, although possible, obviously could not be detected using the study s criteria. The grade of the optic disc and that of the visual field were evaluated at every visit at which they had been performed. The optic discs had been evaluated in the charts at almost every visit, usually at 3- or 6-month intervals; visual field examinations were routinely repeated at about 6-month intervals. When either the optic disc and/or visual field was observed for three consecutive visits to have changed to a more severe stage, the patient s glaucoma was regraded to reflect that new stage. The interval between the baseline examinations and the date that the change was first noted was recorded, and the follow-up variables were abstracted from the patient s record. The mean IOP levels in patients getting worse and in those not getting worse were compared. Because elevation of IOP is believed to precede change in the optic disc or visual field, the IOP measurements used were an average of the IOP at the time the change was first noted and the two IOP measurements preceding that change. The relationship between the deterioration of the glaucoma and the final visual outcome of the patients was evalu- 901

3 Ophthalmology Volume 110, Number 5, May 2003 Table 1. Characteristics of Patients Included in the Study and Their Glaucomas Characteristics N (%) Gender Male 54(52.9) Female 48(47.1) Race White 98(96.1) Black 4 (3.9) Family history of glaucoma Negative 64(62.4) Positive 38(37.6) Systemic diseases Hypertension 55(53.5) Diabetes mellitus 11(10.9) Ischemic heart disease Nonglaucoma ocular diagnosis Myopia ( 3) 78(76.0) Age related macular degeneration 17(17.0) Retinal detachment 2 (2.0) Type of glaucoma Primary open-angle glaucoma 59(57.8) Low-tension glaucoma 18(17.6) Pigmentary glaucoma 17(16.7) Exfoliative glaucoma 8 (7.8) Visual acuity 20/20 or better 46(45.1) 20/25 20/40 42(41.2) 20/40 14(13.9) Grade of glaucomatous optic nerve damage Grade 0 2 (2.0) Grade I 49(48.0) Grade II 31(30.4) Grade III 31(12.7) Grade IV 7 (6.9) Grade V 00 Grade of glaucomatous visual field damage Grade 0 18(17.7) Grade I 38(37.3) Grade II 22(21.6) Grade III 16(15.7) Grade IV 8 (7.8) Grade V 00 Stage of glaucoma at initial presentation Stage 0 00 Stage I 45(44.1) Stage II 31(30.4) Stage III 17(16.7) Stage IV 9 (8.8) Stage V 00 Stage of glaucoma in different diagnostic glaucoma subgroups POAG POAG Stage I 28 Stage II 16 Stage III 9 Stage IV 5 LTG Stage I 4 Stage II 8 Stage III 5 Stage IV 1 PG Stage I 8 Stage II 5 Stage III 2 Stage IV 2 XFG Stage I 4 Stage II 2 (continues) ated (vision was classified as improved or worsened if there was a change of 2 or more lines of Snellen acuity). The principal outcome variable was worsening of glaucoma from one stage to another, based on the grading system of the optic disc and visual field features. Probability of worsening by one or more stages was plotted against length of follow-up as a Kaplan- Meier survival curve for the entire study group and for each of the subgroups with baseline stages ranging from I to IV. The rate of deterioration from one stage to another was estimated graphically as the median time to deterioration. The actuarial rate of worsening by one stage or more was also estimated for each subgroup. Results Table 1. (continued) Characteristics N (%) Stage III 1 Stage IV 1 LTG low-tension glaucoma; PG pigmentary glaucoma; POAG primary open-angle glaucoma; XFG exfoliative glaucoma. One hundred seven charts of patients who had continuously been followed for a minimum of 15 years and whose records were currently active and filed in the chart room of the senior author (GLS) were identified. Of these, 102 patients (102 eyes) met the study criteria, and all were included in the study. The mean age of the patients at baseline examination was years. The mean duration of follow up was years. Mean IOP at time of initial presentation was mmhg. Forty-five (44.1%) of the eyes were not receiving antiglaucoma treatment at their first visit. The remaining 57 were receiving alpha-adrenergic agonists (epinephrine and dipivefrin, 71.6%), miotics (65.7%), beta-blockers (33.3%), and systemic carbonic anhydrase inhibitors (15.4%); 2 of these patients had already had laser trabeculoplasty, and 3 had already had glaucoma filtering surgery. Table 1 shows the demographic and baseline ocular variables, in addition to the grades of glaucomatous changes in the optic disc and visual field and stages of glaucoma at baseline examination. Two eyes (2.0%) had normal optic disc appearance at baseline examination; 18 (17.6%) had normal visual fields. No patient had both normal discs and normal fields. Concentric diffuse damage of the optic nerve was the most common presenting optic disc feature (29 eyes, 28.4%), followed by focal notching of the neuroretinal rim (20 eyes, 19.6%), and vertical cupping (18 eyes, 17.6%). The most common presenting abnormalities of the visual fields were paracentral scotoma (29 eyes, 28.4%), nasal step (20 eyes, 19.6%), and single arcuate defect (18 eyes, 17.6%). Regarding the types of management applied to all 102 patients until the first deterioration was noted, two patients received no therapy other than observation, 33 were treated with glaucoma medications, 23 had laser therapy, and 44 had glaucoma filtering surgery. On the basis of on the combined disc-field grading system, 19 of the eyes did not deteriorate over a mean follow-up period of years, whereas 43 deteriorated one stage, 31 eyes two stages, and 9 eyes three stages. None deteriorated four stages (Table 2). The median time to first deterioration of glaucoma in all patients after initial diagnosis was 7.5 years (95% confidence interval 6.2 and 8.8 years), to second deterioration 18.5 years 902

4 Table 2. Probability of Deterioration by One or More Stages for All Cases and Time Taken to Each Deterioration Deterioration Eid et al Long-term Follow-up of Open-angle Glaucomas Number of Cases Cases That Did Not Deteriorate Count n % Mean Length of Follow-up (yrs) Count Cases That Had Deteriorated Deviation n % Median Time to Diagnosis of Worsening from Baseline (ys) By at least one stage By at least two stages By at least three stages Error (95% confidence interval 15.5 and 21.5 years), and to third deterioration 24.5 years. It should be noted that these figures indicate when the first change was noted, even though a definite change was not considered present until the change had been documented on three successive examinations. The rate of deterioration of the optic disc is illustrated in Figure 1, and the deterioration of the visual field is shown in Figure 2. Four of 9 patients (44.5%) with stage IV glaucoma at baseline evaluation worsened by at least one stage compared with 16 of 17 (94.1%) of those with stage III, 27 of 31 (87.1%) of those with stage II, and 36 of 45 (80.0%) of those with stage I (Table 3, log rank test: P 0.02). The median time to first deterioration in patients who started with stage I glaucoma was 7.5 years, in patients with stage II 6.5 years, in patients with stage III 5.5 years, and in patients with stage IV 14.5 years. On the other hand, 18 (40.0%) with stage I glaucoma at initial diagnosis deteriorated two stages, 16 (51.6%) of the eyes with stage II the same amount, and 5 (29.4%) with stage III that same amount (Table 3, log-rank test: P 0.2). The median time to second deterioration in patients who started with stages I and II glaucoma was 16.5 years, and in patients with stage III 16.5 years. Of the patients initially with stage I glaucoma, 5 (11.1%) worsened three stages (median duration 21 years), whereas 4 (12.9%) presenting with stage II disease worsened three stages (median duration 26 years) (Table 3, log rank test: P 0.6). However, the statistical power to detect change across these stages was low (40%), given the small numbers in these subgroups. At last follow-up, 9 (8.8%) of the patients were stage I, 22 (21.6%) stage II, 26 (25.5%) stage III, 32 (31.4%) stage IV, and 13 (12.7%) stage V. Eleven (18.6%) of the eyes with POAG did not deteriorate over a mean follow-up time of 17.8 years, whereas no eyes (0.0%) having XFG remained stable. The median time to first deterioration for patients diagnosed with POAG and PG was 7.5 years, whereas that for patients with LTG was 5.5 years and that for patients with XFG was 4.5 years. Log-rank test did not show significant values in any of the curves. Table 4 compares the mean values of IOP between the cases that did and those that did not deteriorate. This comparison was made each time a progression to another stage was encountered. There was no significant difference at any point, despite the slightly lower level of IOP in the patients who did not deteriorate. An attempt was made to relate the amount of decrease in IOP noted after the baseline visit with the likelihood of subsequent deterioration. Of the 42 eyes with a reduction of IOP greater than 29%, 35 got worse. In contrast, of the 60 eyes in which there was an IOP reduction of less than 30%, 48 got worse (chi-square analysis showed no significant difference). During the course of follow-up the lens remained clear in 25 cases and became cataractous in 77. Sixty patients had cataract extraction. By the end of follow-up, vision was stable or improved in 50 eyes (49.0%) and worse in the other 52 eyes (51.0%). Figure 3a illustrates the status of visual acuity of the study eyes at final evaluation relative to the stage of glaucoma at initial examination, whereas the bar chart in Figure 3b illustrates this final visual status relative to the baseline visual acuities. Twenty (19.6%) of the eyes had visual acuity 20/200 or worse. The visual acuity of those 20 eyes at baseline evaluation was 20/200 or worse in 3 eyes and better than 20/50 in 11 lives. Five of these eyes started with stage I glaucoma, 6 with stage II, 6 with stage III, and 3 with stage IV. Eight of these 20 eyes ended with stage V glaucoma; 6 had visually significant cataract; 3 had high myopia with macular changes; 2 had age-related macular degeneration; 1 had central retinal vein occlusion. Discussion This study considered the rate of deterioration of glaucoma. This factor, rate of change, is among those that must be considered if treatment is to be appropriate. To our knowledge, few studies have specifically evaluated this critically important aspect of glaucoma. 1,2,6,17,18 One reason there have been so few is that the rate of change of glaucoma is often slow and consequently difficult to study. Another is the absence of an appropriate staging system. We used here, as our primary measure, a method that combines a system of grading the optic disc and the visual field. This system was used to increase the likelihood that a change in the calculated stage of the glaucoma represented a true change in the Figure 1. Kaplan-Meier survival curve indicating rate of deterioration of one stage of the optic disc. 903

5 Ophthalmology Volume 110, Number 5, May 2003 Figure 2. Kaplan Meier survival curve of rate of deterioration of one stage of the visual field. state of the patient s glaucoma. It is known that optic discs in many patients show changes before visual field defects are detectable. Nevertheless, in some cases, visual field changes are noted despite an inability to detect change in the optic disc. In this study, if either the disc or the field showed a change, that was considered to represent a deterioration. Figures 1 and 2 show the rate of deterioration in terms of the optic disc alone (Fig 1) and the visual field alone (Fig 2). The curves are similar, but that for the disc change is slightly more linear. Because of the duration of the study (minimum of 15 years, average of 20 years) and because of evolving methods of visual field examination during those years, all patients had visual field examinations performed by at least two methods (Octopus and Humphrey), and most of the patients in this study had visual field examinations performed by three different methods (kinetic perimetry [Goldmann], Octopus, and Humphrey perimetry). Consequently, it was not possible to use systems such as those developed before various national collaborative trials, such as the Glaucoma Laser Trial, the Advanced Glaucoma Intervention Study, and the Collaborative Initial Glaucoma Treatment Study. The visual field system used is a modification of that developed by Hodapp et al. 20 However, that system is limited to three stages of deterioration and was not designed to detect change but rather to categorize patients with glaucoma roughly into mild, moderate, or advanced stages of damage. As such, the Hodapp-Parrish-Anderson system was not believed to be appropriate for this study, because it would be too insensitive to detect change. Regarding the disc, there are the cup/disc method and two other disc staging systems developed, that by Shiose and Kanda 21 and that by Jonas and colleagues. 22 Shiose and Kanda s system is qualitative and complex and not validated. It requires a breakdown into various subgroups of glaucoma on the basis of the appearance of the optic disc, a method that is not totally accepted. The system of Jonas and colleagues is skewed toward optic nerves with moderate and advanced damage and as such is not capable of monitoring change in the earlier stages of glaucoma. The system used in this study is a second version of one previously used by one of the authors. 19 It was found to be reproducible when evaluated in a masked fashion, as described in the Patients Methods section of this article. In addition, there was a good correlation between disc and field grades (Spearman correlation coefficient, r 0.855). Image analysis systems were not used in this study. Although many of the subjects had disc images captured with the PAR/Topcon ImageNet system, this image analysis system was discarded because of poor reproducibility. Consequently, follow-up examinations using this technology were not obtained. More modern methods were not available 15 years ago. The systems of disc and field grading used in this study, then, are believed to be appropriate, because there were no others available for the purpose of quantitating change. The patients in this study were selected from a referral glaucoma practice and may differ in unknown ways from other populations of patients with glaucoma. Approximately one fifth of the patients in the study did not deteriorate during the follow-up period of almost 20 years. Failure to detect deterioration could be a factor of the sample size in this study. Consequently, all of the following figures regarding rate of deterioration represent minimal estimates; the rates may have been higher: 81.4% worsened by at least one stage, 38.2% by at least two stages, and 8.8% by three stages. The frequency of glaucomatous optic disc deterioration reported by Airaksinen and associates 16 was 79% over a 10-year follow-up period. Hart and Becker 5 found that 73% of eyes with manifest glaucomatous visual field defects deteriorated to dense involvement of the orig- Table 3. Probability of Deterioration of Each Stage of Glaucoma during the Follow-up Interval and the Length of Time Taken to Each Deterioration from Baseline Date No Deterioration Deterioration by at Least One Stage Deterioration by at Least Two Stages Deterioration by at Least Three Stages n Length of Follow-up (yrs) n Time to First Worsening (ys) n Time to Second Worsening (yrs) n Time to Third Worsening (yrs) Mean Deviation Median Error Median Error Stage I (n 45) Stage II (n 31) Stage III (n 17) Stage IV (n 9) Error 904

6 Eid et al Long-term Follow-up of Open-angle Glaucomas Table 4. Comparison of Means of Intraocular Pressure Between Cases That Did Not Deteriorate and Cases That Worsened at Each Time a Worse Stage Was Encountered Intraocular Pressure (mm Hg) n Mean Deviation P Value IOP at baseline Stable cases Cases getting worse IOP at first progression Stable cases Cases getting worse IOP at second progression Stable cases Cases getting worse IOP at third progression Stable cases Cases getting worse IOP intraocular pressure. inally affected altitudinal hemifield over a 10-year follow-up period. Mikelberg et al 3 found 76% of their glaucoma patients showed worsening of visual field defects during a median follow-up period of 8 years, and Zeyen and Caprioli 17 found 8 (53%) of 15 patients with an initially Figure 3. The status of visual acuity of the study eyes at final evaluation relative to (A) the stage of glaucoma at initial examination and (B) their baseline visual acuities. normal visual field showed progression of optic disc damage during a mean follow-up of 6.1 years. Gliklich and coworkers 23 found the rate of field change in a population of low-tension POAG patients was significantly greater than that in a cohort of similar patients with elevated IOP. In our analysis, the percentage of eyes that deteriorated by one or more stages was higher among the patients with stages III (94.1%), II (87.1%), and I (80.0%) glaucoma at the time of initial presentation than it was among those initially diagnosed with stage IV (44.4%). Also, the percentage of eyes that deteriorated two or more stages was higher among the patients with stage II glaucoma at presentation than among those with stage I (52% compared with 40%). This apparent inconsistency may be an artifact or an indication that the grading scale used was not linear (see later). It may also be due to less vigorous treatment of those patients who had less advanced glaucoma, or it may indicate a higher probability of deterioration by more than one stage among patients with more advanced damage than among those with an earlier stage of the disease. This last observation has been reported by other investigators Several authors have suggested that eyes that are diagnosed and treated early in the course of the disease do well; these authors hypothesize that the less-damaged optic nerve is more resistant to further damage and therefore less likely to reach a more advanced stage of deterioration. For example, Zeyen and Caprioli 17 estimated that the mean rate of neuroretinal rim area loss is 1.7% per year in eyes with visual fields that are normal and 2.1% per year in eyes that have visual field loss already present. Chandler 26 reported that eyes with advanced glaucoma in which there is marked cupping of the optic disc and considerable field loss withstand increased tension poorly and require an IOP below average to prevent further loss of visual function. However, these conclusions are speculative. It is certain that not all cases with elevated IOP or even with definite early glaucomatous optic nerve damage will deteriorate further. As already mentioned, few studies of untreated glaucoma exist. A population of cases with early glaucoma is certainly not a homogeneous collection of patients who will get worse. That population consists of a certain (unknown) number of patients who will get worse and a certain (also unknown) number who will not. It is likely that some patients diagnosed as having early chronic glaucoma do not in fact have glaucoma, that is, do not have a disease characterized by a worsening optic neuropathy. In contrast, cases with more advanced glaucoma, such as in stage II, have already demonstrated that they have a disease that is likely to deteriorate. In addition, a correct diagnosis of glaucoma is more likely to occur in patients who have more advanced disease, because the findings tend to be more characteristic in patients with advanced disease than they are in patients with early disease. Consequently, the number of individuals who are misdiagnosed as having glaucoma will probably be smaller in patients with more advanced disease as contrasted with earlier disease. A population of patients with more advanced disease, then, will consist of more cases that are going to continue to deteriorate than will a population composed of less-damaged individuals. The more damaged population, then, will consist 905

7 Ophthalmology Volume 110, Number 5, May 2003 of cases that presumably are predestined to continue to get worse. That more cases with more marked disease tend to get worse, then, may be merely a reflection of the fact that such cases are more predisposed to becoming worse and may be unrelated to the fact that they already have more advanced disease. In our study, the median time to first worsening for eyes presenting with stage IV glaucoma was substantially longer than it was for the other study eyes. The relatively low rate of deterioration (44.4%) and the relatively long interval to deterioration for patients presenting with stage IV glaucoma may be attributed to several factors: first, the tendency of the treating ophthalmologist to treat cases presenting for the first time with advanced disease more aggressively, specifically, by initiating early surgical intervention and attempting maximum reduction of IOP; second, patients faced with advanced disease at initial presentation may be more vigilant and careful in following their ophthalmologist s advice than those with a less serious condition; third, it is possible that the distances between successive grades of either the optic disc or visual field are not equal in terms of number of neurons lost. That is, the number of neurons lost between our arbitrary stages I and II may not be the same as the number lost between stages III and IV. Odberg 27 found that 58% of patients with advanced glaucoma (loss of at least half of the visual field) with an IOP less than 15 mmhg remained stable for a mean follow-up period of 7.6 years. Kolker 7 reported that loss of central vision was rare in patients with glaucomatous visual field loss close to fixation when the mean IOP was maintained below 18 mmhg. Shirakashi and coworkers 15 found that eyes with advanced visual field loss with IOPs less than 15 mmhg during a 15-year follow-up period remained stable, whereas eyes with mean IOPs greater than 15 mmhg showed deterioration. It took a median of 7.5 years after initial presentation for the glaucoma in the patients we studied to deteriorate to the next stage, and another 10 years for it to worsen by another stage. Most previous studies used only visual field changes to determine the rate of worsening of glaucoma. Studies reported deterioration of the visual field ranging from 18% to 86% of patients, with an average of 45%. 1 3,5 7,10,12,15 Although the method of evaluation of the visual field, the method of analysis, and the lengths of follow-up differed among these studies, most of them conclude that approximately half the patients with glaucoma worsened in terms of visual field over a 5-year period. Complicating this deterioration was the finding that in many patients whose visual fields were considered to have worsened, repeat field examinations could not confirm the worsening. Quigley and associates 1 have suggested that the rate of deterioration tends to be overstated unless there are repeated confirmations of field changes. In our study, the rate of deterioration of glaucoma was confirmed by consistently finding signs of worsening in three consecutive visual field tests and/or optic disc examinations. Vision worsened in half of the patients, and approximately 20% had visual acuity of 20/200 or worse at the final evaluation. Of those reaching this stage, causes other than glaucoma were responsible in about 60% of cases. Six of the 20 such eyes had cataract progression, and 6 others had retinal pathology, which was believed to have contributed to the worsening of vision, as well as of the visual field, giving a false impression of glaucoma deterioration. Eleven (44%) of the eyes had vision of 20/50 or better at their initial diagnosis, whereas 75% had definite damage to the optic disc and visual field (stages II to IV). Regardless of the effect on vision, the glaucoma in all the patients whose visual acuity was 20/200 or worse by the end of the study had deteriorated by one or more stages. Eight of these patients ended with stage V glaucoma in which the central field was almost totally affected. Hattenhauer et al 2 estimated the probability of blindness in at least one eye from classic open-angle glaucomas to be 27% at 20 years. This value is higher than what we found. This difference may be attributed to differences in patient selection between the two studies (our patients are from a private tertiary office, whereas those of Hattenhauer et al are community based), and differences in method. If we considered partial or total encroachment of field loss on central fixation (represented by grades IV and V in our grading system) as an indicator of visual field limited to 20 or less, 45 patients (44%) at last follow-up in our study would be included, on the basis of visual field criteria alone (32 with grade IV and 13 with grade V). This value is comparable to that estimated by Hattenhauer et al 2 (50%) for unilateral blindness from chronic glaucoma. No apparent relationship was found between level of IOP and stability or deterioration in this study. The study was not primarily designed to investigate this relationship, and the significance of this finding is uncertain. Our study is limited by the retrospective character required in analyzing such long-term follow-up data, the diversity of the various diagnostic methods used (e.g., manual kinetic vs. automated static perimetry), and the nonstandardized therapeutic regimens used (although most of the patients followed a stepped approach starting with medicinal treatment, then laser trabeculoplasty, and finally filtering surgery). Another limitation is the fact that this group of patients from a tertiary referral office may not represent the average glaucoma population. It is almost certainly different from the population of glaucoma patients followed in the average comprehensive ophthalmologist s office. It would be expected that this population was skewed in the direction of difficult cases. An additional problem is that the size of the pool from which the 102 cases were selected cannot be meaningfully assessed, because an unknown number of patients seen before 1982 were not included, those who may have gone elsewhere or died. Consequently, the actual rate of change may be different from and, presumably, higher than that reported here. Finally, the racial distribution of our population, with predominantly white patients (96%), suggests that our results would not be applicable to glaucoma generally, because the severity of the disease is different in different races. In summary, approximately 80% of patients took 71/2 years to manifest a deterioration of their optic nerve and/or visual field by one full stage, in which a stage represented one step on the way from no damage (stage 0) to far- 906

8 Eid et al Long-term Follow-up of Open-angle Glaucomas advanced damage (stage V). In the cases that worsened by one stage, further worsening took a longer time than the 7.5 years required for the first worsening. Visual acuity was maintained in half of the cases. Of the 17% of eyes that ended with visual acuity of 20/200 or worse, the cause for the poor visual acuity was deterioration of glaucoma in 40%. In 60% of the cases the reduced acuity was due to nonglaucomatous causes. Acknowledgments. The authors wish to thank Dr. James Augsbarger for extensive assistance with the statistics. References 1. Quigley HA, Tielsch JM, Katz J, Sommer A. Rate of progression in open-angle glaucoma estimated from cross-sectional prevalence of visual field damage. Am J Ophthalmol 1996; 122: Hattenhauer MG, Johnson DH, Ing HH, et al. The probability of blindness from open-angle glaucoma. Ophthalmology 1998;105: Mikelberg FS, Schulzer M, Drance SM, Lau W. The rate of progression of scotomas in glaucoma. Am J Ophthalmol 1986; 101: Mao LK, Stewart WC, Shields MB. Correlation between intraocular pressure and progressive glaucomatous damage in primary open-angle glaucoma. Am J Ophthalmol 1991;111: Hart WM Jr, Becker B. The onset and evolution of glaucomatous visual field defects. Ophthalmology 1982;89: O Brien C, Schwartz B, Takamoto T, Wu DC. Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma. Am J Ophthalmol 1991;111: Kolker AE. Visual prognosis in advanced glaucoma: a comparison of medical and surgical therapy for retention of vision in 101 eyes with advanced glaucoma. Trans Am Ophthalmol Soc 1977;75: Leydhecker W, Gramer E. Long-term studies of visual field changes by means of computerized perimetry (Octopus 201) in eyes with glaucomatous field defects after normalization of the intra-ocular pressure. Int Ophthalmol 1989;13: Harbin TS Jr, Podos SM, Kolker AE, Becker B. Visual field progression in open-angle glaucoma patients presenting with monocular field loss. Trans Am Acad Ophthalmol Otolaryngol 1976;81: Kidd MN, O Connor M. Progression of field loss after trabeculectomy: a five-year follow-up. Br J Ophthalmol 1985;69: Sekine M, Araie M, Suzuki Y, Koseki N. Factors contributing to the progression of visual field damage in eyes with normaltension glaucoma. Ophthalmology 1994;101: Gliklich RE, Steinmann WC, Spaeth GL. Visual field change in low-tension glaucoma over a five-year follow-up. Ophthalmology 1989;96: Werner E, Drance SM, Schulzer M. Trabeculectomy and the progression of glaucomatous field loss. Arch Ophthalmol 1977;95: Jay JL, Murdoch JR. The rate of visual field loss in untreated primary open angle glaucoma. Br J Ophthalmol 1993;77: Shirakashi M, Iwata K, Sawaguchi S, et al. Intraocular pressure-dependent progression of visual field loss in advanced primary open-angle glaucoma: a 15-year follow-up. Ophthalmologica 1993;207: Airaksinen PJ, Tuulonen A, Alanko HI. Rate and pattern of neuroretinal rim area decrease in ocular hypertension and glaucoma. Arch Ophthalmol 1992;110: Zeyen TG, Caprioli J. Progression of disc and field damage in early glaucoma. Arch Ophthamol 1993;111: Javitt JC, Spaeth GL, Katz LJ, et al. Acquired pits of the optic nerve. Increased prevalence in patients with low-tension glaucoma. Ophthalmology 1990;97: ; discussion Spaeth GL, Hwang S, Gomes M. Disc damage as a prognostic and therapeutic consideration in the management of patients with glaucoma. In: Gramer E, Grehn F, eds. Pathogenesis and Risk Factors of Glaucoma. Berlin: Springer, 1999; Hodapp E, Parrish RK II, Anderson DR. Clinical Decisions in Glaucoma. St. Louis: Mosby-Year Book, Shiose Y, Kanda T. Quantitative analysis of the optic cup and its clinical applications. Part II. Clinical cases. Jpn J Clin Ophthalmol 1974;28: Jonas JB, Gusek GC, Naumann GOH. Optic disc morphometry in chronic primary open-angle glaucoma. II. Correlation of the intrapapillary morphometric data. Graefes Arch Clin Exp Ophthalmol 1988;226: Gliklich RE, Steinmann WC, Spaeth GL. Visual field change in low-tension glaucoma over a five-year follow-up. Ophthalmology 1989;96: Grant WM, Burke JF Jr. Why do some people go blind from glaucoma? Ophthalmology 1982;89: Fruhauf A, Muller F, Sismuth M. Untersuchungen zur Prognose des Glaukoms. Klin Monstabl Augenheilkd 1967;151: Chandler PA. Long-term results in glaucoma therapy. Am J Ophthalmol 1960;49: Odberg T. Visual field prognosis in advanced glaucoma. Acta Ophthalmol 1987;65(Suppl): Shaffer RN. Open-angle glaucoma. Trans Am Acad Ophthalmol Otolaryngol 1963;67: