G. K. Krieglstein

Quantitative Morphologic and Functional Evaluation of the Optic Nerve Head in Chronic Open-Angle Glaucoma

Glaucoma leads to morphologic changes of the optic nerve head and to functional defects. Morphologic changes in the three-dimensional surface structure of the optic nerve head at its entrance site into the globe can be examined by laser scanning tomography. The standard technique for evaluating functional defects in glaucoma is static computerized perimetry. We compared these two techniques to determine which is more sensitive for follow-up of glaucomatous damage of the optic nerve head. If decreased function is presumed to precede imminent cell death, visual field analysis should be the more sensitive method, as cell death results in absolute defects of the visual field. However, the neuronal networks do not necessarily function in this way. In the case of loss of individual elements in the neuronal network, the complex linkages, even at the retinal level, are able to maintain functions and compensate for loss of function, which means that visual field defects would not be prominent. If the damage increases with time and is accompanied by a progressive loss of ganglion cells, however, compensation is eventually no longer possible, and the functional defects then become measurable by visual field analysis. Thus, morphologic absolute changes may be more prominent than visual field defects in the early stages of glaucoma. To evaluate the quantitative relationship between morphometrically measurable defects of the optic nerve head and measurable functional defects, we first examined the visual field with static computerized perimetry and then evaluated the surface structure with a laser scanning tomograph in 90 patients with chronic open-angle glaucoma, 10 patients with ocular hypertension, and 10 patients without any eye disease. Based on the 95th percentile of the standardized rim/disk area ratio, we calculated the relative rim area loss and correlated this with the mean defect in visual field analysis. The scatterplot shows an exponential curve. In the early stages of glaucoma, visual field defects were less prominent than morphologic absolute changes; 40% of the neuroretinal rim area is lost by glaucomatous optic nerve damage before first defects in visual field analysis appear. In late stages of glaucoma, changes in perimetry are more prominent than those observed with biomorphometry. These results show that in the follow-up of patients with early stages of glaucomatous damage, special attention should be given to morphologic absolute changes. In patients with advanced glaucoma, progress of the damage should be observed by repeated functional, rather than morphologic, examinations. It is important to keep in mind, however, that the sensitivity of any method is dependent on technology. One reason why functional tests may not be as sensitive as morphologic examination in observing patients with early stages of glaucoma may simply be that functional tests are not yet sensitive enough to detect early damage.

Ultrasound biomicroscopy and its value in predicting the long term outcome of viscocanalostomy.

Aims: To examine whether the early postoperative morphology at the site of sclerectomy, as visualised by ultrasound biomicroscopy (UBM), is an indicator of the mechanisms that lower intraocular pressure (IOP) and/or predictors of the long term outcome of viscocanalostomy. Methods: 15 eyes of 14 patients with medically uncontrolled open angle glaucoma and no history of surgery underwent viscocanalostomy according to Stegmann’s technique. Ultrasound biomicroscopy was performed during the first month after surgery. The following parameters were assessed: dimensions of the intrascleral “lake,” presence of a filtering bleb, presence of a subconjunctival cavity or a suprachoroidal hypoechoic area, and the thickness of the residual trabeculocorneal membrane. A complete ophthalmological examination was performed the day before and the day after surgery. Follow up visits were scheduled 1 week, 4 weeks, 6 months, and 12 months after surgery. Results: At 1 year successful control of IOP (<20 mm Hg) was achieved without further manipulation or medication in six of 15 eyes. The size of the intrascleral “lake” (average 0.62 mm3) did not correlate with later IOP; however, a visible route under the scleral flap and accidental perforation of the trabeculocorneal membrane were associated with long term lowering of IOP. Normal thickness of the trabeculocorneal membrane (0.10–0.15 mm) was indicative of IOP control with and without medication. When UBM showed an early collapse of the intrascleral cavity, control of IOP was not achieved. Other UBM findings did not predict long term function. Conclusion: In accordance with previous studies, the authors found that UBM examination is a useful method to evaluate outflow mechanisms after glaucoma surgery. This study shows that UBM imaging of external filtration during the early postoperative period can be used to predict the success of viscocanalostomy. However, to establish conclusively what parameters of UBM predict successful viscocanalostomy a larger number of patients must be studied.

Ganciclovir for the treatment of anterior uveitis

Abstract Background: Ganciclovir, administered systemically or intraocularly, is effective in controlling cytomegalovirus (CMV) retinitis in immunocompromised patients. The efficacy of therapy with this antiviral substance was investigated in an immunocompetent patient with CMV uveitis causing secondary glaucoma. Methods: To identify the presence of an intraocular viral infection, anterior chamber taps to detect the intraocular synthesis of IgG antibodies and PCR testing were carried out. Clinically, the degree of intraocular inflammation and the intraocular pressure (IOP) values were monitored. During this time, the patient was treated systemically with ganciclovir administered orally and intravenously. Results: The intraocular synthesis of IgG antibodies specific for CMV was found in two samples of aqueous humor, but negative for other viruses. PCR testing was negative for HSV, VZV and CMV at each time. During this time, the patient was treated systemically with ganciclovir administered either intravenously or orally. As a response to therapy with ganciclovir, the elevated IOP values decreased to normal and the intraocular inflammation declined. After cessation of ganciclovir administration, the inflammation and secondary glaucoma recurred. Conclusion: In this case of anterior uveitis presumably caused by CMV inducing secondary glaucoma, treatment with ganciclovir led to a decrease of the inflammation and normalization of IOP. It appears that continuous administration may be required to control the infection in an immunocompetent patient.

Morphologic proof of the toxicity of mitomycin C on the ciliary body in relation to different application methods.

Abstract · Background: Since postoperative hypotony has been a frequent complication of glaucomatous filtration surgery with adjunctive use of mitomycin C (MMC), the question arises of whether there may be another application method which can minimize this side effect. The purpose of this study was to establish the morphologic side effects of different application methods. · Methods: MMC 0.2 mg/ml was applied to the episclera of nine eyes of six pigmental rabbits at random via collagen shield (CS), soft contact lens (CL), or lyophilisate (20 µg; LY) for 5 min. Two eyes (controls) had a subconjunctival injection of BSS only. Another control eye was left untreated (no injection). No trabeculectomy was performed. One hour later the amounts of MMC in the conjunctiva and aqueous were analyzed by reverse-phase high-pressure liquid chromatography. Ciliary bodies were dissected from the enucleated eyes, embedded and investigated by transmission electron microscopy (TEM). Cell height of the nonpigmented ciliary epithelium was morphometrically assessed by means of computer-assisted image analysis. · Results: The light-microscopic analysis of the sectioned cell area revealed reduction of the cell height of the non-pigmented ciliary epithelium (NPCE) after application with soft contact lens (foufold) and collagen shield (2.5-fold) but not with lyophilisate compared to the untreated eye. The following ultrastructural changes were seen: loss of apical microvilli (CS, CL, LY), disintegrating melanin granules within NPCE (CS), lysis of entire areas with NPCE cells (CS), myelin figures within mitochondria (LY), intracellular vacuoles (CS, CL), lysis of myelinated nerves (CS), myelin figures in mitochondria of endothelial cells (LY), and lysis of stromal fibrocytes (CS). In the control eyes (injection of BSS) none of these ultrastructural changes were detected in the cylindrical NPCE cells. The concentration of mitomycin in the aqueous humor after topical application of MMC on the episclera for 5 min were all below the detection limit (<10 ng/ml). The concentration of MMC in the conjunctiva ranged from 2.1 to 3.7 µg/g. · Conclusion: Severe morphologic alterations were seen at the electron-microscopic level after application of MMC 0.2 mg/ml with a collagen shield and with a soft contact lens. They were mildest with lyophilisate and absent in the BSS controls. A new administration device is needed if trabeculectomy is to be performed successfully using MMC in human glaucomatous eyes.

A prospective randomised trial of viscocanalostomy with and without implantation of a reticulated hyaluronic acid implant (SKGEL) in open angle glaucoma

Aim: To prospectively assess the efficacy and complications of viscocanalostomy with a reticulated hyaluronic acid implant (VSRHAI) versus standard viscocanalostomy in patients with medically uncontrolled open angle glaucoma. Methods: A consecutive series of 40 patients (40 eyes) with uncontrolled open angle glaucoma underwent non-penetrating antiglaucomatous surgery. After the excision of the deep scleral flap they were randomly assigned to either a standard viscocanalostomy or additional implantation of a reticulated hyaluronic acid implant. Follow up visits were over a period of 12 months after surgery. Results: The mean preoperative intraocular pressure (IOP) was 26.5 (SD 6.1) mm Hg for all patients enrolled. The mean IOP was 8.1 (SD 5.6) mm Hg 1 day after surgery for the viscocanalostomy group (p<0.001) and 12.0 (SD 5.2) mm Hg for the VSRHAI group (p<0.001). The postoperative IOP difference between the two groups was statistically significant (p = 0.03). The success rate, defined as an IOP lower than 22 mm Hg without medication, was 40% in both groups at 12 months postoperatively (p = 0.90). The number of postoperative complications was equally low for both groups. Conclusions: Both surgical procedures, viscocanalostomy and VSRHAI, provide comparable success rates over a 1 year follow up period. The specific intraoperative and postoperative complications of non-penetrating surgery were seen in our series, although the overall rate of postoperative complications proved equally low for both techniques.

Modern concepts in antiglaucomatous implant surgery

BackgroundAntiglaucomatous implant surgery is a continously evolving field in glaucoma treatment.MethodsA literature search with the terms “glaucoma implant surgery”, “aqueous shunts” and “glaucoma drainage devices” was carried out, especially giving prominence to innovative surgical developments in glaucoma implant surgery and to recently established clinical evidence on traditional shunt surgery.ResultsEpiscleral glaucoma drainage devices have recently proven their efficacy in large studies. Longterm data about their clinical efficacy and their risk/safety profile are sufficiently available. New antiglaucomatous devices try to target alternative drainage routes, for example trabecular or uveoscleral outflow. Valid longterm data from prospective randomized clinical trials are not available for these devices as yet.ConclusionsAlthough valid data on clinical application of the new glaucoma implants are not available as yet, profound knowledge about their theoretical concept and their practical management is obligatory for all glaucoma clinicians.

Trabeculectomy: A Retrospective Follow-up of 700 Eyes

A major focus of our study was to determine the value of postoperative intraocular pressure (IOP) in predicting the outcome of trabeculectomy (TE). The medical charts of 547 patients undergoing glaucoma filtering surgery at the Department of Ophthalmology of the University of Cologne from 1987 to 1996 were reviewed. The status of the visual field, level of visual acuity, appearance of the bleb, cup/disc ratio and IOP were studied. Pre- and post-operative glaucoma medication was recorded. The eyes with congenital glaucoma and those treated with anti-metabolites were excluded. The results are presented with particular emphasis being placed not only on intraocular pressure (IOP) control but also on the progression of glaucomatous damage (deterioration of visual field or disc damage) and the decrease of visual acuity. The tonometric success rate of TE in controlling the IOP <21 mmHg was 61%. Defining the rigid criteria for success of trabeculectomy as an IOP <21 mmHg, no further visual field loss, no disc damage and no additionally required surgical intervention due to glaucoma, the success rate decreased to 44%. The results indicate that other factors than normalization of IOP determine the success rate of TE. Should trabeculectomy be the therapy of first choice in the early stage of glaucoma? Should trabeculectomy fail to control the IOP in the first eye, would this allow options, such as the use of antimetabolites in the second eye?

The effect of the water-drinking test on aqueous humor dynamics in healthy volunteers.

In 19 healthy volunteers (9 men, 10 women) we studied the effect of drinking 1000 ml of water within 10 min on aqueous humor dynamics. Fluorescein was applied topically five times, 6 h before measurements. All readings were taken during the afternoon. The Wilcoxon signed-rank test was used to evaluate the statistical relevance of the data. Aqueous humor flow was measured 60 min before (F1) and 10 min (F2), 30 min (F3), 60 min (F4) and 90 min (F5) after drinking 11 of water. Flow (mean ± SD) changed as follows: F1, 2.25 ± 1.2 μll/min ; F2, −3.29 ± 3.4 μ/min (P < 0.0000); F3, 1.69 ± 1.0 gml/min (P=0.007); F4, 2.39±0.9 μl/min (P=0.25); F5, 2.64±0.9 μl/min (P=0.02). Three to four days later the identical procedure was performed in each individual: F1, 2.06 ± 1.0 μl/min F2, −3.12 ± 2.4 μl/min (P < 0.0000); F3, 1.09 ± 0.6 μl/min (P < 0.0001); F4, 1.76 ± 0.6 μl/min (P=0.15); F5, 2.54±0.8 μl/min (P=0.01). The correlation coefficient for the left and night eyes (F1–F5, both days) was r=0.85. The mean flow in the 19 healthy volunteers during the afternoon hours was 2.25 ± 1.0 μl/min. Water load consistently led to a reflux of unbound fluorescein into the eye about 10 min later. This is documented as a negative flow. Ninety minutes after drinking 1000 ml of water there is a significant increase in flow, which is in contrast to the normal diurnal curve of aqueous humor dynamics. Water load causes hydremia and an increase in episcleral venous pressure. Fluorophotometry together with water load may be useful to study the aqueous humor dynamics in healthy and glaucomatous eyes and eyes with ocular hypertension.

Reproducibility of circadian retinal and optic nerve head blood flow measurements by Heidelberg retina flowmetry

Background/aim: The Heidelberg retina flowmeter (HRF) is designed to measure retinal capillary blood flow. Previous studies however showed weak reproducibility of data. The intraindividual reproducibility of circadian HRF measurements was examined in healthy subjects in three locations of the retina. Methods: 36 healthy volunteers (27.3 (SD 4.3) years) were examined by HRF seven times a day (t0–t6). Using a default window of 10×10 pixels, three consecutive measurements were performed in three precise focusing planes: superficial, intermediate and deep layer, peripapillary retina, neuroretinal rim and cup, respectively. Images of identical tissue locations identified by capillary landmarks of each layer were selected to quantify the retinal microcirculation of each volunteer. Means and standard deviations of all flow results of a given subject were calculated, at t0–t6 and the coefficients of variation as a measure of reproducibility. Results: The coefficients of variation ranged between 8.4% and 41.0% in the superficial layer (mean 19.8% (SD 8.4%)), 10.6%, and 43.0% in the intermediate layer (mean 24.0% (SD 8.4%)), and 9.9% and 84.0% (mean 29.6% (SD 15.8%)) in the deep layer. Conclusions: These data show the best reproducibility of measurements in the superficial layer followed by the intermediate and the deep layer. Clinically, this is an unsatisfactory intraindividual reproducibility of flow values in each studied layer.

Photodynamic modulation of wound healing in glaucoma filtration surgery

Aim: To report a clinical pilot study investigating photodynamic therapy (PDT) in combination with glaucoma filtration surgery. BCECF-AM was used as the photosensitising substance. The clinical safety and tolerability of BCECF-AM, and its efficacy in controlling postoperative intraocular pressure (IOP) were assessed. Methods: Before trabeculectomy (TE), 42 consecutive eyes of 36 glaucoma patients received one subconjunctival injection of 80 μg BCECF-AM (2,7,-bis- (2-carboxyethyl) -5- (and-6) -carboxy-fluorescein, acetoxymethyl-ester) followed by an intraoperative illumination with blue light (λ = 450–490 nm) for 8 minutes. Antifibrotic efficacy was established as postoperative IOP reduction of >20% and/or an IOP constantly < 21 mm Hg without antiglaucomatous medication. Follow up of the filtering bleb was documented by slit lamp examination. Results: Eyes had mean 1.1 preoperative surgical interventions (filtration and non-filtration glaucoma surgery). Mean preoperative IOP was 31.6 (SD 9.7) mm Hg. Patients were followed for mean 496 days (range 3.5–31.8 months). Of the 42 eyes, 25 eyes had an IOP decreased to 15.8 (3.4) mm Hg without medication (complete success: 59.5%; p<0.001; t test). Seven eyes showed good IOP reduction < 21 mm Hg under topical antiglaucomatous medication (qualified success: 16.7%). 10 eyes failed because of scarring within 2–67 weeks (23.8%). Clinical follow up examinations revealed no local toxicity, no uveitis, and no endophthalmitis. Conclusions: This method is a new approach in modulating postoperative wound healing in human eyes undergoing glaucoma filtration surgery. The data of the first human eyes combining TE with PDT underline the clinical safety of this method and its possible potential to prolong bleb survival.