[Glaucoma Session in Hamburg 1999. Early diagnosis of glaucoma and normal-pressure glaucoma in clinical practice].
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OBJECTIVE: To provide the results of the Early Manifest Glaucoma Trial, which compared the effect of immediately lowering the intraocular pressure (IOP), vs no treatment or later treatment, on the progression of newly detected open-angle glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred fifty-five patients aged 50 to 80 years (median, 68 years) with early glaucoma, visual field defects (median mean deviation, -4 dB), and a median IOP of 20 mm Hg, mainly identified through a population screening. Patients with an IOP greater than 30 mm Hg or advanced visual field loss were ineligible. INTERVENTIONS: Patients were randomized to either laser trabeculoplasty plus topical betaxolol hydrochloride (n = 129) or no initial treatment (n = 126). Study visits included Humphrey Full Threshold 30-2 visual field tests and tonometry every 3 months, and optic disc photography every 6 months. Decisions regarding treatment were made jointly with the patient when progression occurred and thereafter. MAIN OUTCOME MEASURES: Glaucoma progression was defined by specific visual field and optic disc outcomes. Criteria for perimetric progression were computer based and defined as the same 3 or more test point locations showing significant deterioration from baseline in glaucoma change probability maps from 3 consecutive tests. Optic disc progression was determined by masked graders using flicker chronoscopy plus side-by-side photogradings. RESULTS: After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P =.007) and occurred significantly later in treated patients. Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status. Although patients reported few systemic or ocular conditions, increases in clinical nuclear lens opacity gradings were associated with treatment (P =.002). CONCLUSIONS: The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss.
Glaucoma represents one of the most common eye diseases and is characterized by progressive loss of visual fields. In the more advanced stages bilateral blindness may result, due to optic nerve atrophy and an excavated optic nerve head. Open-angle glaucoma is one of the main disease subsets, which may be further divided into high tension primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Recently, the optineurin ( OPTN) gene was identified as a causative factor for NTG. Alterations in this gene were found in Caucasian families with NTG. In particular, c.458G>A, c.691-692insAG and c.1944G>A were shown to be risk factors. Since NTG is reported to be the most common form of glaucoma in Japan, and to identify if the OPTN gene plays a role in POAG, the DNAs from 148 unrelated Japanese patients with NTG, 165 patients with POAG and 196 unrelated controls who were not suffering glaucoma were investigated by appropriate genotyping techniques. No glaucoma-specific mutations were found in the OPTN gene in Japanese glaucoma patients. However, some novel single-nucleotide polymorphisms (SNPs) in the exons and introns are reported in this paper for the first time.
PURPOSE: To report the clinical outcome in 48 eyes of 48 children who received a Baerveldt glaucoma implant (BGI) for the management of pediatric glaucoma. DESIGN: Retrospective, noncomparative case series. METHODS: The medical records of all patients with pediatric glaucoma who underwent a BGI at two tertiary care referral centers in Los Angeles between 1990 and 1999 were reviewed. Intraocular pressure (IOP), intraoperative and postoperative complications, number of glaucoma medications, visual acuity, and pre- and postoperative corneal diameter and axial length were collected from patient records. Criteria for success were IOP between 6 and 21 mm Hg with or without glaucoma medications, no need for further glaucoma surgery, the absence of visually threatening complications, and some residual vision (minimum visual acuity of light perception). RESULTS: The study included 48 eyes from 48 patients aged 16 years and younger (mean age 4.1 years). Mean preoperative IOP was 31.2 +/- 25.7 mm Hg, and mean postoperative IOP was 16.4 +/- 4.9 mm Hg. Cumulative probability of success (based on the Kaplan-Meier survival curve) was 95% at 6 months, 90% at 1 year, 84% at 2 years, 74% at 36 months, and 58% at 48 months. On average, the BGIs were successful for a mean period of 5.6 years (67.7 months). Overall, 11 eyes failed, with the causes being uncontrolled IOP (eight eyes), retinal detachment (two eyes), and no light perception (one eye). CONCLUSIONS: Baerveldt glaucoma implants can be a safe and effective treatment modality for the management of pediatric glaucoma refractive to medical therapy.
PURPOSE: To evaluate the efficacy of the Ahmed Glaucoma Valve implant in refractory glaucomas in Indian eyes. MATERIALS AND METHODS: A retrospective review was conducted on the charts of 122 eyes of 122 patients with refractory glaucoma treated with Ahmed Glaucoma Valve implant placement at Guru Nanak Eye Centre, New Delhi between January 1996 and December 1999. The main outcome measure was success at the last follow-up. Success was defined as an intraocular pressure (IOP) of 22 mmHg or less and 5 mmHg or more and at least a 30% reduction in IOP without visually devastating complications or additional glaucoma surgery. RESULTS: The mean postoperative IOP (17.29+/-3.79 mmHg) was significantly (P<0.001) lower than the mean preoperative IOP (31.47+/-7.86 mmHg) at last follow up (mean 12.51+/-8.37 months; range 3-24 months). The cumulative probability of success by Kaplan-Meier analysis was 85.95% at 12 months and 82.83% at 24 months. The mean number of postoperative antiglaucoma medications (0.75+/-0.80) was also significantly lower (P<0.001) than the mean preoperative number of antiglaucoma medications (2.83+0.72). The most common complication was corneal-tube contact, which occurred in five (4.10%) eyes. Retinal detachment occurred postoperatively in one eye with the clinical diagnosis of neovascular glaucoma secondary to Eale's disease. Two patients had tube extrusion requiring repositioning and reinforcement with scleral patch graft. CONCLUSIONS: Ahmed Glaucoma Valve implantation is an effective and relatively safe therapy for the treatment of refractory glaucoma in Indians.
OBJECTIVES: To establish the relative safety and effectiveness of trabecular aspiration in combination with phacoemulsification and intraocular lens (IOL) implantation (asp+IOL) for decreasing intraocular pressure (IOP), and to compare the outcome of this method of treatment with that of phacoemulsification and IOL implantation alone (IOL-alone) or standard filtering glaucoma triple procedure (triple procedure). DESIGN: Prospective, controlled study randomized with respect to assignment to trabecular aspiration, with a case-control design between the asp+IOL and triple procedure groups. PARTICIPANTS: Seventy-four eyes of 74 patients with uncontrolled pseudoexfoliation glaucoma without a history of previous intraocular or extraocular surgery and in need of cataract surgery. Forty-eight patients were randomized to those receiving adjunctive trabecular aspiration (asp+IOL group of 26 eyes) and those given no trabecular aspiration (IOL-alone group of 22 eyes). The triple procedure group consisted of 26 cases, closely matched to the asp+IOL cases in terms of age, sex, cup-disc ratio, glaucoma medication requirements, and systemic diseases. INTERVENTIONS: Temporal clear corneal phacoemulsification and foldable IOL implantation was performed in all eyes. In the asp+IOL group, trabecular aspiration was performed with a suction force of 100 to 200 mm Hg under light tissue-instrument contact using a modified intraocular aspiration probe. A modified Cairns-type trabeculectomy without adjunctive antimetabolites was performed superiorly in the triple procedure eyes after IOL implantation. MAIN OUTCOME MEASURES: Surgical outcome was assessed in terms of IOP change, need of adjunctive glaucoma medication, visual acuity outcome, and complications. Surgical failure was defined as an outcome requiring additional surgical intervention or more than 1 medication to achieve IOP control to the target pressure. RESULTS: Two years after surgery, success rates were 36%, 64%, and 78% in the IOL-alone, asp+IOL, and triple procedure groups, respectively (P<.001). Hyphema (46%) and ocular hypotony (11%) were observed in the triple procedure group only, whereas blood reflux (61%) and descemetolysis (19%) were seen exclusively in the asp+IOL group. CONCLUSIONS: In pseudoexfoliative eyes, asp+IOL is significantly more effective than cataract surgery alone in reducing postoperative IOP and the necessity for glaucoma medication. Although trabecular aspiration in the triple procedure did not achieve pressure control in all patients, especially in the low target pressure range, the risk profile appears to be more favorable in the trabecular aspiration-treated eyes than in the filtering glaucoma triple procedure group. Trabecular aspiration in the glaucoma triple procedure could serve as a possible first-line treatment for pseudoexfoliative eyes with coexisting cataract and glaucoma.
OBJECTIVES: To investigate the prevalence of myocilin (MYOC) mutations in Italian families with glaucoma and to determine the relationship of these mutations to primary open-angle glaucoma (POAG), juvenile open-angle glaucoma (JOAG), and pigmentary dispersion glaucoma. METHODS: Twenty-six patients with POAG were selected based on a positive family history of glaucoma. All patients and 210 relatives had an accurate clinical characterization. MAIN OUTCOME MEASURE: Each index patient was screened by single-stranded conformational polymorphism analysis for mutations in the MYOC gene. RESULTS: A MYOC gene mutation was found in 2 families. In one family, a previously reported p.K423E mutation was transmitted from the index patient with POAG to the 2 sons with JOAG. In the second family, a p.C25R change, affecting the signal peptide, was transmitted from the index patient with POAG to the son with JOAG, but not to the son with pigmentary dispersion glaucoma. CONCLUSIONS: Clinical characterization of 2 families with MYOC gene mutations indicates that POAG and JOAG are the 2 sides of a continuum phenotypical spectrum due to a common molecular defect. On the other hand, our results confirm the different origin of pigmentary dispersion glaucoma. CLINICAL RELEVANCE: Because MYOC gene mutations may be responsible for a fraction (2 [8%] of 26) of families with POAG/JOAG, a molecular genetic diagnosis should be included in the management of patients with glaucoma.
PURPOSE: Determine patients' understanding of glaucoma and its treatment, their sources of information about glaucoma, their preferences for treatment, their experience with medication side effects, and their reasons for changing eye doctors. DESIGN: Prospective, nonrandomized patient survey study. METHODS: A questionnaire was developed and sent to the 22,000 subscribers of the Gleams newsletter who have glaucoma. RESULTS: Questionnaires were returned by 4310 glaucoma patients. Most respondents received glaucoma information from their eye doctor. Only 28% of respondents reported having changed eye doctors for reasons related to their glaucoma. Of those who had, 60% cited poor communication as the reason. When queried about specific side effects associated with their medication, over 85% of responding patients were never or rarely bothered by headaches and eyelid darkening. Most respondents (67% and 55%, respectively) were rarely or never disturbed by red eye or burning and stinging. Most respondents understood the importance of intraocular pressure (IOP) lowering in glaucoma, and of those patients who expressed a preference, 92% reported that they would prefer the medication that lowers IOP the most, even if it caused red eye for a few weeks, over a medication that caused no red eye but did not get IOP as low. CONCLUSIONS: Patients who subscribe to Gleams and responded to the survey rely most on their doctors for information about glaucoma and its treatment. Most understand the importance of maintaining low IOP to decrease the risk of vision loss, and most will tolerate temporary ocular side effects to achieve low IOP.
PURPOSE: A 1986-1987 survey found 8.8% prevalence of open-angle glaucoma in the black population of St. Lucia, West Indies. This follow-up study assessed visual field loss progression in untreated glaucoma patients and glaucoma suspects 10 years later. DESIGN: Cohort study. METHODS: Subjects were 205 glaucoma patients and suspects; 1987 data included age, sex, visual acuity, and visual fields measured by automated threshold perimetry (Humphrey C 30-2 test), and 1997 data included intraocular pressure, visual acuity, and visual fields measured by the same test. Exclusion criteria included field unreliability, field improvement due to vision improvement, nonglaucomatous vision deterioration, glaucoma treatment since 1988, and scoring of a visual field as end stage in 1987. Visual fields were scored by algorithms for the Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study (CIGTS). RESULTS: By AGIS criteria, 55% of 146 right eyes and 52% of 141 left eyes showed progression of visual field loss. In linear regressions, progression severity was unassociated with sex, intraocular pressure, or baseline visual field score, but was positively associated with age (P <.001, right; P =.002, left). The cumulative probability of reaching end stage in 10 years in at least one eye was approximately 16% by AGIS criteria. By CIGTS criteria, 73% of 146 right eyes and 72% of 141 left eyes progressed. CONCLUSIONS: These data provide a unique opportunity to study progression of untreated glaucoma. The percentage of eyes showing visual field loss progression and the percentage reaching end stage were considerably higher than in studies of visual field progression in treated eyes.
OBJECTIVE: To assess the prevalence of primary angle-closure glaucoma (PACG), the frequency of its different clinical presentations, and its association with peripheral anterior chamber depth in a defined population in Northern Italy. DESIGN: Cross-sectional epidemiologic study in a defined population. PARTICIPANTS: All subjects resident in the Egna-Neumarkt area of the South Tyrol Region (Northern Italy) and more than 40 years of age were invited to undergo an ophthalmologic examination. INTERVENTION: After the screening examination, subjects with suspected glaucoma were re-examined at the screening center to confirm the diagnosis. All cases that still proved suspect after the second examination underwent a third phase of investigations and were classified as healthy or as definitely glaucomatous. Each subject was examined according to a standard protocol, including medical history interview, refraction and visual acuity determination, ocular biomicroscopy, evaluation of peripheral anterior chamber depth by means of the Van Herick method, applanation tonometry, optic disc evaluation, and computerized perimetry. Gonioscopy was not performed during initial screening but only in all selected patients in the second and third phases of investigations. The diagnosis of PACG was made on the basis of the concomitant presence of at least two of the following criteria: intraocular pressure > or = 22 mmHg, glaucomatous optic disc abnormalities, glaucomatous visual field defects. In addition, biomicroscopic or gonioscopic evidence of angle closure was also necessary. MAIN OUTCOME MEASURES: Percentage distribution of peripheral anterior chamber depths, prevalence of angle-closure glaucoma, and frequency of the different PACG clinical presentations. RESULTS: Four thousand two hundred ninety-seven subjects were examined (73.9% overall participation rate). The peripheral depth of the anterior chamber according to the Van Herick method was grade 2 in 14.7%, grade 1 in 2.5%, and grade 0 in 0.3% of the population. The overall prevalence of angle-closure glaucoma was 0.6% (26 cases). Five of these were cases of previous acute attacks resolved by therapy, three were cases of chronic angle-closure after acute attacks, three were intermittent angle-closure glaucomas, and 15 were chronic angle-closure cases. CONCLUSIONS: Occludable angles were more frequent than in other white populations previously studied. The prevalence of PACG is not as low as is usually believed; this type of glaucoma accounts for more than a quarter of all glaucomas found in the Egna-Neumarkt population. The most frequent clinical presentation is chronic angle-closure glaucoma.
OBJECTIVE: This study aimed to demonstrate specific morphologic patterns in congenital glaucoma after various surgical procedures by means of ultrasound biomicroscopy (UBM) and to investigate correlations between UBM morphology and the effectiveness of glaucoma surgery in reducing intraocular pressure. DESIGN: Observational case series. PARTICIPANTS AND INTERVENTIONS: Thirty four eyes of 18 consecutive patients, not older than 18 years, with congenital glaucoma and with a history of previous antiglaucomatous surgery underwent UBM examination of the anterior chamber angle in the treatment area and in an untreated region. MAIN OUTCOME MEASURES: The morphology of the anterior chamber angle region and the tissue reflectivity were analyzed. RESULTS: Specific UBM patterns of the anterior chamber angle in congenital glaucoma were observed after goniotomy, trabeculotomy, trabeculectomy, deep sclerectomy, and cyclodialysis. In the first months after surgery, a limited correlation was found between morphology and the success of filtering surgery. Adhesions of the iris or the ciliary processes to the trabeculectomy cleft were detected in 19 of 25 eyes after filtering procedures. CONCLUSIONS: In cases of cloudy cornea and unknown previous glaucoma surgery, UBM can be used to identify the type and localization of previous surgery in congenital glaucoma, thus assisting surgical planning for subsequent glaucoma management. The correlation between UBM morphology and the effectiveness of filtering surgery is less convincing than previously demonstrated in adults, possibly underlining the importance of individual nonsurgical factors for prognosis in congenital glaucoma.
Atrophy of the optic nerve is associated with changes of the retinal fiber layer (RNFL). Using red-free photographs the authors examined the RNFL of 398 eyes with chronic primary open-angle glaucoma and compared it with the RNFL of 234 normal eyes. The glaucoma group was divided into five stages and the fundus into four sectors. Differences between the normal and glaucoma eyes were: (1) The sequence of the sectors, with regard to the best visibility of the retinal nerve fiber bundles, was changed. In the normal eyes the nerve fiber bundles were most often best visible in the inferior temporal sector, followed by the superior temporal sector, the temporal horizontal area and finally the nasal region. In the glaucoma group the nerve fiber bundles were significantly more often best detectable in the superior temporal sector and the temporal horizontal area. (2) The degree of visibility of the retinal nerve fibers decreased significantly with increasing glaucoma stage. (3) Localized defects were seen in 15% of the eyes with glaucoma and none of the normal eyes. The specificity of this qualitative parameter was, therefore, 100%. The defects were found most often in the superior and inferior temporal regions. These differences between normal and glaucomatous eyes were also significant for the first glaucoma stage of this study. The localization of the foveola below the optic disk center (0.53 +/- 0.34 mm in the glaucoma group and 0.55 +/- 0.29 mm in the normal eyes) was not significantly different.
PURPOSE: The aim of this study is to report costs, detection rates, and resources needed for detection of primary open angle glaucoma and related diseases in a glaucoma screening program in Salzburg, Austria, over a period of 8 years. METHODS: The Salzburg-Moorfields Collaborative Glaucoma Study performed a complete ophthalmologic examination on a total of 4864 subjects within a study period of approximately 8 years (98 months). The total numbers reported are total number of subjects screened at the initial examination and follow-up examinations; total working hours and estimated working hours per visit for one ophthalmologist and two medical assistants; direct costs per visit; detection rates for subjects; and corresponding costs per true positive case diagnosed with definite primary open angle glaucoma (POAG), early POAG, POAG suspect, ocular hypertension (OHT), and glaucoma artefact. RESULTS: Within the screening period of 98 months, a total of 9427 examinations and second verification checks were performed: 5466 at the initial examination, 404 at the 1-year follow-up, 815 at the 2-year follow-up, 339 at the 3-year follow-up, 225 at the 4-year follow-up, 1059 at the 5-year follow-up, 996 at the 6-year follow-up, 118 at the 7-year follow-up, and 5 at the 8-year follow-up. The total amount of time spent for screening was 23,814 working hours. We estimate the costs per visit at EUR 123 for each initial examination, EUR 28 for each second confirmation check, and EUR 95 per follow-up examination. The following detection rates were observed: definite POAG: 1.7% (95% CI: 1.3-2.2%), early POAG: 2.9% (95% CI: 2.3-3.5%), POAG suspect: 8.5% (95% CI: 7.6-9.4%), OHT: 2.2% (95% CI: 1.7-2.7%), glaucoma artefact or other causes: 5.8% (95% CI: 5.1-6.6%), normal cases: 79% (95% CI: 78-80%). CONCLUSIONS: Direct costs per visit were considerably higher than those reported in the Netherlands or the United Kingdom. If a health care provider decides to perform a glaucoma screening within this setting, the costs for the detection of a new case are EUR 7250 for definite POAG, EUR 4250 for early POAG, EUR 1450 for POAG suspect, EUR 5600 for OHT, EUR 2100 for glaucoma artefact case, and EUR 156 for a normal case.
Glaucoma causes more blindness and disability than any other eye disease except for cataract. Cataract surgery is highly successful, even intracapsular cataract surgery. The major problem, then, with regard to relieving or preventing disability related to cataract is one of access to care. Though access to care is a major problem with glaucoma, it is by no means the only problem. Many patients with glaucoma get worse, even when they are being treated. Additionally, it is not only glaucoma itself that causes disability. In the recent past, far more damage was caused by treatment for glaucoma than by glaucoma itself. To repeat, summarized slightly differently, glaucoma and its treatment damage health more than any other eye disease except cataract, and the medical profession is responsible for a major part of that problem. How can it be that glaucoma and its treatment still cause so much disability? In the first place, care is unavailable in many areas, and, second, care is not utilized even where available, and third, care is often inappropriate even where available. The first two issues are of great importance but are not the subject of this discussion. It is my belief that the major explanation for why care is often poor is because the goals of care are often wrong. Specifically, the goals of care are to lower intraocular pressure, or to prevent visual field loss. These may be appropriate intermediary steps on the way to achieving the appropriate goal, but they are not the goal itself.
The need for more sensitive tests for the early detection of compromised visual function in glaucoma is established by anatomic and psychophysical evidence of damage occurring to optic nerve fibers in eyes with normal visual fields. The results are reported of temporal frequency testing on 51 glaucoma suspects without visual field loss in either eye, 52 glaucoma patients with visual field deficits in the tested eye, and 11 normal subjects. Modulation transfer functions were obtained using a sinusoidally flickering 5 degrees spatially uniform white field viewed with central fixation and plotted at six frequencies from 5-30 Hz. The results showed a frequency-specific sensitivity loss centered at 15 Hz and a nonfrequency-specific mean sensitivity loss, that was greater, on average, in glaucoma patients than in suspects. Sensitivity losses of both kinds were seen in most glaucoma patients, but only in a minority of glaucoma suspects. About 12% of suspects were indistinguishable from the lowest performing one third of these glaucoma patients. A smaller number of suspects appeared to form a second mode in the frequency distribution for temporal sensitivity at 15 and 25 Hz. In patients with glaucoma, age was found to be a significant factor associated with the magnitude of mean sensitivity loss. Age was not a significant factor contributing to sensitivity loss in individual suspect data as measured by regression analysis, but it contributed to a small and consistent sensitivity loss across frequency for group-averaged data in those older than 55 years of age.
Color vision changes may occur early in the course of glaucoma and may precede visual field loss. Glaucoma suspects, having raised intraocular pressure and no diagnostic optic nerve head or visual field changes, may also have color vision loss. Unfortunately, the instruments used in the studies that have demonstrated these color vision changes were not feasible for routine clinical use; likewise, the studies did not carefully control for the effects of small pupil size and age or did not point to the underlying mechanisms responsible. We studied 19 glaucoma patients, 19 glaucoma suspects, and age-matched controls for each group by means of the Farnsworth D-15 panel test, a desaturated version of the D-15 test, and by measures of spectral increment threshold. Minor modifications of the Farnsworth D-15 panel test produce highly significant differentiation of glaucoma and glaucoma-suspect patients from age-matched normal groups. Further, spectral increment thresholds, with a two-degree spectral target flashed at either 1 or 25 Hz on a bright white background, show that both achromatic and chromatic sensitivity are significantly reduced when compared with their age-matched normals. Pupil size does not seem to be a significant factor. These results suggest that the function of two different ganglion cell populations is affected in glaucoma and that glaucoma may produce functional loss in the central foveal area earlier in the disease process than previously believed.
The optic disc topography of 11 eyes of 11 glaucoma-like discs without increased intraocular pressure or visual field loss was compared with that of 11 eyes of 11 relative early stage normal-tension glaucomas. There were no statistically significant differences between the two groups in terms of optic disc parameters measured with a Rodenstock Optic Nerve Head Analyzer Plus, except that the inferior quadrant of the neuroretinal rim area of the normal-tension glaucoma discs was significantly smaller than that of the glaucoma-like discs. Also, in the Humphrey automated visual field, only the superior part of the Total Deviation score of normal-tension glaucoma eyes corresponding to the inferior disc changes was significantly lower than that of glaucoma-like discs. When the data of the two groups were pooled, the inferior quadrant of the neuroretinal rim area significantly correlated with the visual field loss in the group of eyes with a rim area smaller than 0.198 mm2. These results seem to suggest that some of the glaucoma-like discs might be early normal-tension glaucoma.