Gottfried O. H. Naumann

Pseudoexfoliation syndrome for the comprehensive ophthalmologist. Intraocular and systemic manifestations.

BACKGROUND Renewed interest in pseudoexfoliation syndrome (PEX) may be attributed to an increased awareness of many clinical risks not only for open-angle glaucoma and its recent recognition as a generalized disorder. This review summarizes the range of intraocular and extraocular manifestations. Involvement of all tissues of the anterior segment of the eye results in a spectrum of intraocular complications that have management implication for all practicing ophthalmologists. DESIGN The study design was a review. METHODS Clinical diagnosis depends on biomicroscopy, biocytology, and laser-tyndallometry. Laboratory research methods range from light and electron microscopy, to immunohistochemical and molecular biologic approaches. OBSERVATIONS Clinical-histopathologic correlations focus on the involvement of lens (PEX-phacopathy), zonular apparatus (zonulopathy), ciliary body (cyclopathy), iris (iridopathy), trabecular meshwork (trabeculopathy), and cornea (corneal endotheliopathy) leading to the following complications: (1) open-angle glaucoma as well as angle-closure glaucoma due to pupillary and ciliary block; (2) phacodonesis, lens dislocation, and increased incidence of vitreous loss in extracapsular cataract surgery caused by alterations of the zonular apparatus and its insertion into the ciliary body and lens; (3) blood-aqueous barrier breakdown (pseudouveitis), anterior chamber hypoxia, iris stromal hemorrhage, pigment epithelial melanin dispersion, poor or asymmetric pupillary dilatation, and formation of posterior synechiae due to involvement of all cell populations of the iris; and (4) early diffuse corneal endothelial decompensation explained by a damaged and numerically reduced endothelium. CONCLUSIONS In view of the multitude of clinical complications, PEX is of relevance to comprehensive ophthalmologists, including specialists in glaucoma, cataract, cornea, neuro-ophthalmology, and retina. Special attention to the risks associated with PEX is advised before, during, and after surgery.

Optic disc morphometry in chronic primary open-angle glaucoma. I. Morphometric intrapapillary characteristics.

Four hundred twenty-seven optic discs of 233 unselected patients suffering from chronic primary open-angle glaucoma were morphometrically evaluated and compared with the optic nerve heads of 253 unselected normal subjects. Only one randomly chosen eye per patient was taken into consideration. We found that glaucoma leads to a change in the characteristic configuration of the neuroretinal rim that in normal eyes is significantly (P < 0.001) largest at the lower disc pole, smaller at the upper and nasal disc side, and smallest in the temporal disc region. Based on this information, significant (P < 0.001) morphometric differences between “early” glaucomatous and normal discs are: (a) the neuroretinal rim area in the lower temporal disc sector is smaller than in the upper temporal disc sector; the smallest rim width is outside the horizontal temporal disc sector (“pathognomonic”); the quotient of horizontal to vertical c/d ratio is lowered; and (d) the lower temporal, upper temporal, and total rim area are decreased. No significant difference in overall optic disc size and form exists between normal and glaucomatous eyes. Smaller optic nerve heads are not more susceptible to glaucoma.

Optic disk morphometry in high myopia

The optic nerve head in highly myopic eyes is distinctly different from normal optic disks. We performed magnification-corrected morphometry of photographs of 51 optic nerve heads in highly myopic eyes (myopic refraction of more than −8.00 diopters). Mean refraction was −15.49 ± 5.76 diopters (range, −8.00 to 28.00 diopters), mean age 63.0 ± 12.1 years (range, 27–87 years). The disks were significantly (P < 0.000001; Wilcoxon-Mann-Whitney test) larger and more ovally configurated than 457 unselected normal optic nerve heads with a myopic refraction of less than −8.00 diopters. Refraction, size of the disk, and area of the parapapillary region with chorioretinal atrophy were significantly (P < 0.00001) correlated with each other. The parapapillary vessel diameter was independent from the disk size. Highly myopic disks can be regarded as secondary acquired macrodisks, the size of which is correlated with refraction and possibly age. They should be differentiated from secondary, acquired macrodisks in congenital glaucoma and from primary macrodisks. As in normal eyes, the parapapillary vessel caliber can be used to estimate the optic disk size in relative and approximately absolute units.

Nonmechanical corneal trephination with the excimer laser improves outcome after penetrating keratoplasty1

OBJECTIVE To assess the impact of nonmechanical trephination on the outcome after penetrating keratoplasty (PK). DESIGN Prospective, randomized, cross-sectional, clinical, single-center study. PATIENTS A total of 179 eyes of 76 females and 103 males, mean age at the time of surgery 50.6 +/- 18.5 (range, 15-83) years. Inclusion criteria were (1) time interval from October 1992 to December 1997; (2) one surgeon (GOHN); (3) primary central PK; (4) Fuchs dystrophy (diameter, 7.5 mm) or keratoconus (diameter, 8.0 mm); (5) graft oversize, 0.1 mm; (6) no previous intraocular surgery; and (7) 16-bite double-running diagonal suture. INTERVENTION In a randomized fashion, eyes were assigned either to trephination with the 193-nm Meditec excimer laser (manually guided beam in patients, automated rotation device of artificial anterior chamber in donors) along metal masks with eight orientation teeth/notches (EXCIMER: 53 keratoconus, 35 Fuchs dystrophy; mean follow-up, 37 +/- 16 months) or with a hand-held motor trephine (Microkeratron; Geuder) ( CONTROL 53 keratoconus, 38 Fuchs dystrophy; mean follow-up, 38 +/- 14 months). Subjective refractometry (trial glasses), standard keratometry (Zeiss), and corneal topography analysis (TMS-1; Tomey) were performed before surgery, before removal of the first suture (15.2 +/- 4.2 months), and after removal of the second suture (21.4 +/- 5.6 months). MAIN OUTCOME MEASURES Keratometric and topographic net astigmatism as well as refractive cylinder; keratometric and topographic central power; best-corrected visual acuity (VA); surface regularity index (SRI), surface asymmetry index (SAI), and potential visual acuity (PVA) of the TMS-1. RESULTS Before suture removal, mean refractive/keratometric/topographic astigmatism did not differ significantly between EXCIMER (2.5 +/- 1.8 diopters [D]/3.4 +/- 2.8 D/4.7 +/- 3.1 D) and CONTROL groups (3.0 +/- 1.8 D/3.7 +/- 2.4 D/4.3 +/- 2.1 D). After suture removal, respective values were significantly lower in the EXCIMER group (2.8 +/- 2.0 D/3.0 +/- 2.1 D/3.8 +/- 2.6 D) than in the CONTROL group (4.2 +/- 2.4 D/6.1 +/- 2.7 D/6.7 +/- 3.1 D) (P < 0.0009). In the EXCIMER versus CONTROL group, mean VA increased from 20/100 versus 20/111 (P > 0.05) before surgery, to 20/31 versus 20/38 before (P = 0.001) and to 20/28 versus 20/39 (P < 0.00001) after suture removal. Mean spherical equivalent was significantly less myopic in the EXCIMER group before (-0.9 +/- 3.6 D vs. -2.6 +/- 3.4 D) (P = 0.01) and after suture removal (-1.4 +/- 3.1 D vs. -2.4 +/- 3.5 D) (P = 0.02). Mean SRI (P = 0.04) and PVA (P = 0.007) were significantly more favorable in the EXCIMER versus CONTROL group after suture removal (0.91 +/- 0.45 and 0.82 +/- 0.15 vs. 1.05 +/- 0.46 and 0.73 +/- 0.18). CONCLUSIONS Postkeratoplasty results seem to be superior using nonmechanical excimer laser trephination. Thus, this methodology is recommended as the procedure of first choice in avascular corneal pathologies requiring PK.

Count and density of human retinal photoreceptors.

This investigation was directed at determining the count and regional distribution of photoreceptors in the eyes of 21 human cornea donors aged between 2 and 90 years. Mean count of rods was 60 123 000 ±12907000, and mean cone count was 3173000 ± 555000. Determined 40 μm away from the foveola, cone density measured 125 500 cones/mm2. Extrapolating the distribution curve, cone concentration in the foveal center can be assumed to be about 150 000 cells/mm2 to 180 000 cones/mm2. Towards the retinal periphery, cone density decreased from 6000 cones/mm2 at a distance of 1.5 mm from the fovea to 2500 cells/mm2 close to the ora serrata. Comparing different fundus regions, cone concentration was significantly highest in the nasal region. Cone diameter increased from the center towards the periphery. At a distance of 40 μm away from the foveola, it measured about 3.3 μm, and in the outer retinal regions about 10 μm Rod density was highest in a ring-like area at a distance of about 3–5 mm from the foveola with a mean of 72 246 ± 17 295 cells/mm2. Rod density peaked at 150 000 rods/mm2. It decreased towards the retinal periphery to 30 000–40 000 rods/mm2. Rod diameter increased from 3 μm at the area with the highest rod density to 5.5 μm in the periphery. The hexagonal rod and cone inner segments were regularly arranged in a honey-comb fashion.

The retinal nerve fiber layer in normal eyes.

The retinal nerve fiber layer is different in normal and glaucomatous eyes. The authors used red-free photographs to examine the retinal nerve fiber layer in 234 normal eyes. The retinal nerve fiber layer was most visible in the inferior temporal arcade, followed by the superior temporal arcade, then by the temporal macular area, and finally the nasal area. This distribution was significantly (P less than 0.0001) correlated to (1) the configuration of the neuroretinal rim, which was significantly broadest at the inferior disc pole followed by the superior one, (2) the juxtapapillary caliber of the retinal vessels, which were significantly wider in the inferior temporal arcade than in the superior temporal arcade, and (3) the location of the foveola 0.53 +/- 0.34 mm inferior to the middle point of the vertical optic disc axis. The retinal nerve fiber layer decreased with age. No correlation occurred with sex or right or left eye. No localized retinal nerve fiber layer defects were seen. These features of the normal retinal nerve fiber layer are important for diagnosis of retinal nerve fiber layer changes secondary to optic nerve damage in the diseased eye.

A Histopathologic Study of Zonular Instability in Pseudoexfoliation Syndrome

A weak zonular apparatus has been postulated to account for the high incidence of phacodonesis, lens dislocation, and vitreous complications during extracapsular cataract surgery in eyes with pseudoexfoliation syndrome. To clarify and localize the cause of zonular weakness, we examined 11 eyes with pseudoexfoliation syndrome by using scanning and transmission electron microscopy. The production of pseudoexfoliation material by both the nonpigmented ciliary epithelium and the pre-equatorial lens epithelium resulted in typical alterations of the zonules at three levels. (1) At their origin and anchorage in the ciliary body, the zonular bundles were separated from the disrupted basement membrane of the nonpigmented epithelium by intercalating pseudoexfoliation fibers. (2) In the pars plicata of the ciliary body, pseudoexfoliation material infiltrated the zonular bundles passing alongside the ciliary processes leading to zonular rupture. (3) At their attachment to the anterior lens capsule, the zonular lamella was focally lifted and subsequently ruptured by pseudoexfoliation masses erupting through the capsular surface. The immunohistochemical demonstration of lysosomal enzymes within pseudoexfoliation aggregates indicates that proteolytic mechanisms facilitate zonular disintegration. Ophthalmologists treating eyes with pseudoexfoliation syndrome should be aware of these alterations.

Retinal nerve fiber layer thickness in human eyes

Abstract · Background: A study was carried out to measure the thickness of the retinal nerve fiber layer (RNFL) at the optic disc border. · Methods: RNFL thickness at the optic disc border was histomorphometrically measured on histological sections of 22 human eyes with normal optic nerves and 21 human eyes with absolute secondary angle-closure glaucoma. For three eyes with normal optic nerves, serial sections through the whole optic disc area were available. · Results: In the eyes with normal optic nerves, the RNFL at the optic disc border showed a double hump configuration with the highest mean thickness in the inferior quadrant (mean ± S.D: 266±64 µm), followed by the superior quadrant (240±57 µm), the nasal quadrant (220±70 µm), and finally the temporal quadrant (170±58 µm). In the three globes with serial sections, RNFL was thickest at the inferior disc pole (397±58 µm), followed by the superior disc pole (313±38 µm), the nasal disc pole (165±19 µm), and finally the temporal disc pole (131±15 µm). In the eyes with absolute glaucoma, mean thickness of the remainder of the RNFL was 40±18 µm with no marked differences between the disc regions. · Conclusions: In normal eyes, the RNFL shows a double hump configuration with its thinnest part at the temporal disc pole, followed by the nasal disc pole and the superior disc pole. RNFL is thickest at the inferior disc pole. In glaucomatous optic neuropathy, the inner limiting membrane moves backward about 60–100 µm at the temporal disc border, and more than 200 µm at the inferior and superior disc poles.

Pseudoglaucomatous physiologic large cups

Using planimetric analysis of stereoscopic optic disk photographs, we studied 21 optic nerve heads of 11 subjects who shared the common feature of optic cups that were larger than the mean + 2 S.D. within the normal population. A comparison of these findings to those of 571 normal optic disks and 706 optic nerve heads in eyes with chronic primary open-angle glaucoma showed the following morphologic characteristics: (1) abnormally large optic disk area (mean +/- S.D., 4.49 +/- 0.56 mm2), (2) large cup/disk ratios with the horizontal ratio (0.78 +/- 0.03) significantly (P less than .001) larger that the vertical (0.71 +/- 0.03), (3) increased incidence of cilioretinal arteries, (4) normal neuroretinal rim area (2.06 +/- 0.35 mm2), (5) normal neuroretinal rim configuration, inferiorly (0.43 +/- 0.08 mm) broader (P less than .001, Wilcoxon test) than superiorly (0.33 +/- 0.06 mm), smallest (P less than .0001) temporally (0.20 +/- 0.04 mm), (6) normal form of zone alpha (irregular hypopigmentation and hyperpigmentation) of the parapapillary chorioretinal atrophy with its widest extension in the temporal horizontal area, (7) no zone beta (visible large choroidal vessels and sclera), (8) normal caliber of the parapapillary retinal vessels, and (9) normal parapillary retinal nerve fiber layer. These characteristics are helpful in the differentiation of primary and secondary large cups.

Angiogenesis in corneal diseases: histopathologic evaluation of 254 human corneal buttons with neovascularization.

PURPOSE Angiogenesis in corneal diseases can necessitate corneal transplantation and induce graft rejection. The aim of this study was to find out the histopathologic prevalence of angiogenesis in human corneas removed during keratoplasty, to establish the histopathologic diagnoses most commonly associated with angiogenesis, and to evaluate the anatomic location of new corneal vessels. METHODS Corneal buttons (2,557) after keratoplasty were sent to and analyzed in our ophthalmopathology laboratory between 1992 and 1996. Of these, 1,278 full-thickness and lamellar corneal buttons were randomly retrieved and evaluated in this study. RESULTS Of 1,278 human corneal buttons obtained by keratoplasty, 254 (19.9%) showed angiogenesis. Associated histopathologic diagnoses were (a) scarring after keratitis (109, 45.4%); (b) graft rejection and insufficiency (73, 30.4%); (c) acute necrotizing ulcerative keratitis (30, 12.5%); and (d) scarring after mechanical or chemical injuries (28, 11.7%). Histopathologically, new vessels were usually associated with corneal edema or inflammatory cells or both (76%). The most common locations of new vessels were the upper and middle third of the corneal stroma. Only 11% of new vessels were located solely in the deep stromal layers. CONCLUSION Angiogenesis is a common histopathologic feature of corneal diseases leading to corneal transplantation and was found in 19.9% of excised human corneal buttons. Systemic or topical antiangiogenic therapy could reduce the need for corneal transplantation and retransplantation.