Hemorrhages with optic nerve drusen. A differentiation from early papilledema.

The distinction between early papilledema and drusen of the optic disk may be made more difficult by the presence of hemorrhages. We report five patients with drusen of the optic disk and associated hemorrhages. The distinguishing characteristics of both conditions are described.

The long-term effects of 5-fluorouracil and sodium butyrate on human Tenon's fibroblasts.

The use of subconjunctival 5-fluorouracil (5-FU) in the first weeks after filtration surgery may ensure long-term bleb survival despite a continuing proliferative stimulus such as in eyes with neovascular glaucoma. In addition, long-term side effects may occur, such as increasing bleb thinning. To ascertain the long-term effects of 5-FU and sodium butyrate, an agent with differentiating and antiproliferative properties, we exposed proliferating human Tenon's capsule fibroblasts to different concentrations of the drugs. The cells were exposed to 5-FU for 1-12 d. The cells were subsequently observed for up to 30 d. Cell proliferation was assessed using cell counting and bromodeoxyuridine uptake, and cell viability was assessed with trypan blue uptake. 5-FU and sodium butyrate inhibited fibroblast proliferation during the treatment period. Higher concentrations of 5-FU (100 and 1000 micrograms/ml) for as little as 1 d resulted in no significant increase in the number of fibroblasts for at least 29 d after treatment was stopped, despite continued stimulation with serum. When treatment with sodium butyrate was stopped, there was greater recovery of proliferation. At a constant concentration of 1000 micrograms/ml of 5-FU for 3 or more days, or a concentration of 100 mmol/l sodium butyrate for 12 d, the entire fibroblast population gradually died over the 30 d period. Thus, short-term treatment with 5-FU may result in long-term inhibition of proliferation of fibroblasts. Long-term inhibition depends on the duration of treatment or on the concentration of 5-FU. Short-term treatment may be affecting the ability of the tissues at the bleb site to heal in the long term. Different dosage regimens may have advantages and are discussed.

Scaling the hill of vision: the physiological relationship between light sensitivity and ganglion cell numbers.

PURPOSE: Differential light sensitivity (DLS) in white-on-white perimetry is used as a measure of ganglion cell function to estimate the amount of neuronal damage in glaucoma. The physiological relationship between DLS and ganglion cell numbers is poorly understood. Within small retinal areas, brightness information is summated, so that A * L = C, or A = C/L, where A is target area, L is threshold luminance, and C is a constant. In larger illuminated areas, as with a Goldmann size III target in perimetry, summation is incomplete, so that A(k) = C/L, where k is the coefficient of summation, and 0 < k < 1. This study tests the hypothesis that the target area (A) can be represented by the number of underlying ganglion cells (G) to give G(k) = C/L. METHODS: Normative human data for ganglion cell density within 30 degrees of retinal eccentricity were taken from the literature and corrected for lateral displacement of ganglion cells from the fovea to estimate ganglion cell receptive field density (g). The number of ganglion cell receptive fields within a Goldmann size III target (G) was calculated from target area (A) and receptive field density (g) [G = A (g)]. Normative data for DLS in the central 30 degrees (Humphrey 30-2) were taken from the literature. The coefficient summation (k) was measured empirically at each Humphrey 30-2 test point in 8 normal subjects. The relationship between DLS and G was investigated by plotting DLS as decibels (dB) against G and DLS as 1/L (1/Lamberts) against G(k). The physiological relationship was extrapolated to glaucomatous ganglion cell loss by calculating hypothetical cell losses for 3 and 6 dB sensitivity defects at each test point. RESULTS: Spatial summation increased with eccentricity. The relationship between DLS (dB) and G was curvilinear. The relationship between DLS (1/L) and G(k) was linear (r2 = 0.73). The extrapolation to glaucomatous ganglion cell loss indicated that a proportionally greater loss of ganglion cells is required in the central compared with peripheral visual field for equal losses in dB sensitivity. CONCLUSIONS: The number of underlying ganglion cells, adjusted for local spatial summation, is better reflected by the DLS scale of 1/L than by dB. If spatial summation is unchanged in glaucoma, this scale more accurately reflects the amount of neuronal damage.

Changing views on open-angle glaucoma: definitions and prevalences--The Rotterdam Study.

PURPOSE: To create a quantitative basis for diagnostic criteria for open-angle glaucoma (OAG), to propose an epidemiologic definition for OAG based on these, and to determine the prevalence of OAG in a general white population. METHODS: Of the 7983 subjects 55 years of age or older participating in the population-based Rotterdam Study, 6756 subjects participated in the ophthalmic part of this study (6281 subjects living independently and 475 in nursing homes). The criteria for the diagnosis of OAG were based on ophthalmoscopic and semiautomated Imagenet estimations of the optic disc such as vertical cup-to-disc ratio (VCDR), minimal width of neural rim, or asymmetry in VCDR between both eyes, and visual field testing with kinetic Goldmann perimetry. All criteria for the diagnosis of OAG were assessed in a masked way independently of each other. RESULTS: Mean VCDR on ophthalmoscopy was 0.3 and with Imagenet 0.49, and the 97.5th percentile for both was 0.7. The prevalence of glaucomatous visual field defects was 1.5%. Overall prevalence of definite OAG in the independently living subjects was 0.8% (95% confidence interval [CI] 0.6, 1.0; 50 cases). Prevalence of OAG in men was double that in women (odds ratio 2.1; 95% CI 1.2, 3.6). Different commonly used criteria for diagnosis of OAG resulted in prevalence figures ranging from 0.1% to 1.2%. CONCLUSIONS: The overall prevalence of OAG in the present study was comparable to most population-based studies. However, prevalence figures differed by a factor of 12 when their criteria for OAG were applied to this population. A definition for definite OAG is proposed: a glaucomatous optic neuropathy in eyes with open angles in the absence of history or signs of secondary glaucoma characterized by glaucomatous changes based on the 97.5 percentile for this population together with glaucomatous visual field loss. In the absence of the latter or of a visual field test, it is proposed to speak of probable OAG based on the 99.5th or possible OAG based on the 97.5th percentiles of glaucomatous disc changes for a population under study.

Chemotactic activity of aqueous humor. A cause of failure of trabeculectomies?

The chemoattractant activity for ocular fibroblasts of the aqueous humor of patients undergoing glaucoma surgery was evaluated in 48-well microchemotaxis chambers and compared with control specimens from patients undergoing cataract extractions. All specimens were chemoattractant, but those from patients who had previously undergone glaucoma surgery that had failed were of significantly greater activity than the controls'. This chemoattractant activity is primarily chemotactic. It consists of heat-stable and heat-labile components. The predisposition of a patient to sustain failed glaucoma drainage surgery may be related to the chemoattractant activity of his aqueous humor, since strongly chemoattractant aqueous humor may encourage fibrosis at the operation site.

Serous retinal detachment following glaucoma filtering surgery.

We report the occurrence of serous retinal detachment in association with choroidal effusion and hypotony in six eyes that had undergone glaucoma filtering surgery. Hypotony with choroidal effusion was documented in five patients before the onset of serous retinal detachment. While one patient underwent vitrectomy, treatment was conservative in the other patients. Serous retinal detachment and choroidal effusions resolved spontaneously as the intraocular pressure normalized. Although one patient regained preoperative visual acuity, all other patients lost at least one line of Snellen acuity.

Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile.

OBJECTIVE: To determine the effect of various long-term topical antiglaucoma regimens on the cell population profile of the conjunctiva. METHODS: Conjunctival biopsy specimens from 124 patients undergoing filtration surgery were assessed quantitatively by light microscopy. Preoperatively, the patients had used a drug for only a brief period (group A; n = 28), a beta-blocker alone (group B; n = 31), a beta-blocker in combination with a miotic (group C; n = 33), or a combination of beta-blocker, miotic, and sympathomimetic (group D; n = 32). RESULTS: The conjunctiva in groups A and B was similar. Group C conjunctiva differed, but the changes were most marked in biopsy specimens from patients in group D, where there was a significant decrease in goblet cells (P < .05); increase in pale cells, macrophages, and lymphocytes within the epithelium (P < .001); and increase in fibroblasts (P < .001), macrophages (P < .001), mast cells (P < .05), and lymphocytes (P = .01) in the substantia propria. In addition, the effect of duration of therapy was assessed. Administration of topical medication for more than 3 years was found to increase the numbers of pale cells within the epithelium (P < .05); fibroblasts (P < .05), macrophages (P < .001), lymphocytes (P < .01), and mast cells (P = .001) within the superficial substantia propria; and the numbers of fibroblasts (P = .01) and macrophages (P < .05) within the deep substantia propria. CONCLUSIONS: The compared treatment regimens affected the conjunctiva to different degrees, with multiple-drug topical therapy exerting the greatest effect on the degree of subclinical inflammation within the conjunctiva. The results also indicated that administration of topical medication, irrespective of type, for 3 years or more induced a significant degree of subclinical inflammation.

Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery.

OBJECTIVE: To determine the effect of long-term topical antiglaucoma therapy on the results of glaucoma filtration surgery and to relate any differences to the cell population profile of the conjunctiva. METHODS: Filtration surgery was performed in 124 patients (trabeculectomy in 112 and triple procedures [trabeculectomy, cataract extraction, and intraocular lens implantation] in 12), and the outcome of these procedures was assessed after a minimum follow-up of 6 months. A conjunctival biopsy specimen was obtained at the time of surgery. The patients were divided into four groups according to the type of topical therapy administered. The duration of therapy tended to be greater for the patients treated with a greater number of medication types. The outcome of trabeculectomy was assessed in 106 of the patients. RESULTS: In comparison with the briefly treated-primary surgery group, the success rate of trabeculectomy (90% [n = 28]) was similar to that in the group treated with beta-blockers (93% [n = 29]). The trabeculectomy success rate for patients treated with beta-blockers and miotics was significantly lower (72%, P < .01 [n = 29]), and that for the group treated with beta-blockers, miotics, and sympathomimetics was even lower (45%, P < .001, [n = 20]). CONCLUSIONS: Various treatment regimens were associated with differential effects on the success rate of trabeculectomy. Long-term topical combination therapy was identified as a significant risk factor for failure of trabeculectomy. Preoperative conjunctival cell counts from patients whose trabeculectomies were successful were compared with those whose trabeculectomies failed. Failure was associated with significantly more pale cells (P < .01), macrophages (P < .05), and lymphocytes (P < .05) in the epithelium; fibroblasts (P < .05) and macrophages (P < .05) in the superficial substantia propria; and both macrophages and lymphocytes in the deep substantia propria (P < .01). Thus, preoperative subclinical conjunctival inflammation induced by previous topical medication was identified as a risk factor for failure of trabeculectomy.

Glaucoma and the iridocorneal endothelial syndrome.

The records of 66 patients with the iridocorneal endothelial (ICE) syndrome were retrospectively reviewed. Glaucoma occurred in 33 (50%) of the patients with ICE syndrome and was most common in the variants in which abnormal cells involve the entire posterior corneal surface (disseminated ICE and total ICE). Of 25 patients with glaucoma, the diagnosis of ICE syndrome was overlooked initially in 17 (68%). Medical glaucoma treatment was generally ineffective. Of 22 patients (88%) who underwent surgery (typically trabeculectomy), 10 (45%) required more than one procedure. The success rates of first operations at 1 and 5 years were 60% and 21%, and those of second and third operations at 1 year were 20% and 17%. During the course of their management, 11 patients (44%) developed visual field loss. The diagnosis of ICE syndrome should be considered in younger patients with unilateral glaucoma and confirmed by specular microscopy. Management of glaucoma due to ICE syndrome is surgical, and means of improving its long-term success need to be addressed.

Reversal of topical antiglaucoma medication effects on the conjunctiva.

OBJECTIVE: To determine whether the adverse effects of antiglaucoma medications could be reversed before filtration surgery, potentially reducing the risk of subsequent failure. METHODS: One month before surgery, 30 patients who were receiving multiple antiglaucoma medications underwent an inferior bulbar conjunctival biopsy, ceased using sympathomimetic drops, and began treatment with topical corticosteroid, (1% fluorometholone four times daily). At the time of surgery two conjunctival biopsy specimens were obtained, one from the operation site (superior bulbar region), and one from the inferior bulbar region. The biopsy specimens were quantitatively analyzed by light microscopy. In addition, the outcome of first trabeculectomy for 16 of these patients was compared with that of 16 matched patients who had not undergone an altered preoperative regimen of topical therapy. RESULTS: During a 1-month period a notable decrease occurred in the number of fibroblasts and inflammatory cells throughout the conjunctiva. Inferior bulbar conjunctiva was found to be representative of superior bulbar conjunctiva with respect to these changes. Furthermore, evidence comparing the matched patients suggested that the altered preoperative regimen may have improved the success rate of trabeculectomy. CONCLUSIONS: The preoperative regimen used reversed the adverse conjunctival effect of topical medication. The regimen may be of clinical benefit in improving the success rate of trabeculectomy.

Surgery for refractory glaucoma. Results and complications with a modified Schocket technique.

A consecutive series of 55 eyes of 50 patients who received silicone tube implant surgery is reviewed. Seven patients had neovascular glaucoma and 43 had refractory nonneovascular glaucoma, for which previous surgery was unsuccessful. A minimum follow-up of one year (mean, 18 months) was achieved for 30 eyes of 30 patients. For these eyes, the success rate (as defined by an intraocular pressure of 25 mm Hg or less, with or without medication) was 80%. Visual acuity was maintained or improved in 67% of eyes. The complications encountered in the overall study of 55 eyes are discussed, and six main causes of failure are identified. These include exposure of the silicone tube from erosion of the overlying conjunctiva; blockage of the proximal orifice of the tube; corneal decompensation secondary to tube touch; extrascleral tube compression proximal to the gutter; blockage of the distal orifice of the tube beneath the gutter; and insufficient aqueous absorption from the encapsulated area surrounding the 360 degrees encircling gutter. Revision surgery was required in 21 eyes (38%). Two alternative methods for insertion of the silicone tube (a "cyclodialysis approach" and a "trabeculectomy approach") are described, and their complications are compared. The incidences of tube exposure, choroidal detachment, and flat anterior chambers were far higher in the trabeculectomy group. The cyclodialysis group had an increased incidence of hyphema and corneal endothelial touch by the tube.

The influence of prior therapy on the success of trabeculectomy.

The role of early surgery in the management of primary open angle glaucoma is under debate. To determine whether previous medical therapy influences the outcome of subsequent trabeculectomy, we retrospectively reviewed the results of surgery in two groups of patients. The first group underwent primary trabeculectomy, having had an average of 2 weeks of preoperative medical therapy, and this group was compared with a group of patients who had received at least 1 year of topical glaucoma therapy before undergoing trabeculectomy (the multiple-treatment group). The two groups were similar in terms of a number of variables, including race, age, sex, presenting intraocular pressures, and presenting visual fields, and they differed only in the known duration of their disease. The success rate of trabeculectomy was significantly higher in the primary trabeculectomy group as compared with that in the multiple-treatment group (P less than .001). We discuss the possible reasons for this difference and its implications for the future management of primary open angle glaucoma.

Color vision defects in ocular hypertension and glaucoma. Quantification with a computer-driven color television system.

In order to detect early defects of color vision caused by increased intraocular pressure, a computer graphics device and color monitor system were used to measure color contrast sensitivity. The system determines the threshold chrominance of a colored grating in which there is no change in luminance. The study included 13 control subjects aged 10 to 57 years and 19 patients with ocular hypertension or glaucoma aged 20 to 58 years. In the 13 eyes with visual field loss, color contrast sensitivity was profoundly reduced when the grating colors fell on a tritan color confusion line. In the eyes without visual field loss, tritan color contrast sensitivity was reduced to an average level considerably below the extreme limits of the control group. These results were compared with those of other color vision tests and diagnostic criteria for glaucoma. The findings suggest that among the tests used, color contrast sensitivity testing was able to discriminate most effectively between patients who had retinal damage and the normal population.

Clinical risk factors for failure in glaucoma tube surgery. A comparison of three tube designs.

We studied a cohort of 165 eyes that had undergone tube implant surgery for glaucoma, with a minimum follow-up of 12 months (range, 12 to 72 months). Of the 57 cases (34.5%) in which surgery failed to control intraocular pressure (less than 22 mm Hg), 15 (26%) occurred by 3 months, 36 (63%) by 12 months, and 46 (80%) by 24 months. Cox regression modeling was used to evaluate independent risk factors in the absence of additional therapy. The use of a two-piece (anterior chamber-to-encircling band) tube system was associated with a 2.4 times higher risk of failure (P less than .001) compared with a one-piece system. Neovascular glaucoma was associated with a 2.1 times higher risk of failure (P less than .037) than other types of glaucoma. Late failure of tube implant surgery is common and there is a steady attrition rate over a 2-year follow-up period.

The pattern electroretinogram (PERG) in ocular hypertension and glaucoma.

Studies of normal subjects and of patients with optic nerve disorders suggest that one of the components of the pattern electroretinogram (PERG), the second negative wave, is related to optic nerve function and appears to be diminished even when the condition is relatively mild, with little alteration of visual acuity. It is known that significant loss of nerve fibers may occur prior to the development of visual field loss. We have investigated the PERGs of a group of subjects with early glaucoma and ocular hypertension, comparing them with normal subjects, and have found a selective reduction in the second negative wave in patients with evidence of optic nerve dysfunction. The PERG may prove helpful in discriminating those patients with ocular hypertension who are destined to develop visual field loss unless medical or surgical therapy were to be employed.

Severity and stability of glaucoma: patient perception compared with objective measurement.

OBJECTIVE: To elucidate the relationship between the subjective assessment in patients with glaucoma of (1) the severity of their visual loss, and (2) any deterioration in their visual function and their objective visual fields as measured by computed perimetry. DESIGN: First, patients completed a questionnaire relating to perceived visual disability and underwent binocular visual field testing. Second, a separate group of patients answered a question about perceived visual deterioration: their monocular visual field tests were analyzed retrospectively by pointwise linear regression to establish stability or deterioration. SETTING: The Glaucoma Service of a specialist eye hospital, which is a tertiary referral center and serves the local community. SUBJECTS: One hundred twenty-three patients with glaucoma including 62 for the severity arm of the study and 61 for the progression arm. MAIN OUTCOME MEASURES: Questionnaire responses, Esterman binocular disability score, and objective visual field deterioration. RESULTS: Questions strongly associated with Esterman binocular disability scores related to bumping into things, problems with stairs, and finding things that have been dropped. There was a strong association between perceived visual deterioration and measured bilateral visual field deterioration (P<.01). CONCLUSIONS: There is a strong association between some types of perceived visual disability and the severity of binocular field loss. A patient who notices gradual visual deterioration is twice as likely to have bilateral visual field deterioration as not. The findings in this sample of patients with mild-to-moderate glaucoma challenge the belief that glaucoma is an insidious process in which the symptoms do not appear until the end stage of the disease.

Initial treatment of glaucoma: surgery or medications.

Should surgery or medications be the initial therapy for primary open angle glaucoma? In this set of articles, Drs. Sherwood, Migdal, and Hitchings present evidence suggesting that filtration surgery provides better intraocular pressure control than does medical treatment, good (or better) visual field preservation, and visual acuity as good as that in medically treated fellow eyes. They also cite cost effectiveness, quality of life, and possible adverse effects of medical treatment on future surgery. Drs. Sharir and Zimmerman, on the other hand, favor initial medical therapy, questioning the validity of some reports on surgical results, citing the risks of complications, and noting recent and current progress in the development of antiglaucoma medications. Dr. Schultz' editorial evaluates both points of view, concluding that additional prospective randomized tests may be useful and that either approach may be a viable option, as long as it is individualized to each particular patient.

Local effects of previous conjunctival incisional surgery and the subsequent outcome of filtration surgery.

PURPOSE: Previous ocular surgery involving conjunctival incision is a risk factor for failure of filtration surgery. To determine whether using adjunctive antimetabolite therapy may have a rational basis, a study was performed to determine whether the conjunctival cellular profile was altered by such surgery. METHODS: After a mean follow-up of 5.9 years, filtration surgery outcomes for 35 patients who had undergone conjunctival incisional surgery were retrospectively compared with 29 control and 18 matched patients who had not undergone such surgery. At the time of filtration surgery, a conjunctival biopsy specimen was obtained from all 82 patients, and these were quantitatively analyzed by light microscopy in a prospective manner. RESULTS: Trabeculectomy success for the control group (93%) was significantly higher than for the previous surgery group (38%) (P < .001). Compared with control tissue, conjunctiva from the patients who had undergone previous surgery contained more fibroblasts (P < .001, P < .05), macrophages (P < .01, P < .001), and lymphocytes (P = .001, P < .01) in both superficial and deep substantia propria (respective P values). Furthermore, trabeculectomy failure was associated with an increase in number of conjunctival fibroblasts in intraoperative specimens. CONCLUSIONS: Previous ocular surgery involving the conjunctiva increases the number of conjunctival fibroblasts and inflammatory cells. This may account for the increased risk of trabeculectomy failure. Perhaps on this basis, the use of adjunctive medication may be justified in patients who have undergone previous ocular surgery involving conjunctival incision.

Diffuse visual field loss in chronic open-angle and low-tension glaucoma.

We examined 37 eyes of 37 patients with chronic open-angle glaucoma and 24 eyes of 24 patients with low-tension glaucoma. All patients had a scotoma confined to the upper or lower hemifield. Eyes with open-angle glaucoma showed twice as much loss of sensitivity in the spared hemifield as compared to eyes with low-tension glaucoma. These differences were statistically significant.

Glaucoma screening in the elderly.

Glaucoma is a major cause of visual loss in the elderly and early identification and adequate treatment at least delay progression and reduce visual morbidity. Screening the elderly for chronic simple glaucoma is most required to identify those patients at risk and allow their referral to an ophthalmologist. Screening methods involving checks on intra-ocular pressure, visual field and the optic disc are discussed. It is suggested that, if these were carried out, many glaucoma patients would be discovered amongst the elderly population and with effective treatment ophthalmologists would have progressed a long way towards the aim of preventing blindness occurring from this disease.