Wolfgang A. Schrems

Contralateral Clinically Unaffected Eyes of Patients With Unilateral Infectious Keratitis Demonstrate a Sympathetic Immune Response

PURPOSE To analyze the contralateral unaffected eyes of patients with microbial keratitis (MK) for any immune cell or nerve changes by laser in vivo confocal microscopy (IVCM). METHODS A prospective study was performed on 28 patients with MK, including acute bacterial, fungal, and Acanthamoeba keratitis, as well as on their contralateral clinically unaffected eyes and on control groups, which consisted of 28 age-matched normal controls and 15 control contact lens (CL) wearers. Laser IVCM with the Heidelberg Retinal Tomograph 3/Rostock Cornea Module and Cochet-Bonnet esthesiometry of the central cornea were performed. Two masked observers assessed central corneal dendritiform cell density and subbasal corneal nerve parameters. RESULTS The contralateral clinically unaffected eyes of patients with MK demonstrated significant diminishment in nerve density (15,603.8 ± 1265.2 vs. 24,102.1 ± 735.6 μm/mm²), total number of nerves (11.9 ± 1.0 vs. 24.9 ± 1.2/frame), number of branches (1.7 ± 0.2 vs. 19.9 ± 1.3/frame), and branch nerve length (5775.2 ± 757.1 vs. 12,715.4 ± 648.4 μm/mm²) (P < 0.001 for all parameters) compared to normal controls and CL wearers. Further, dendritiform cell density in the contralateral unaffected eyes was significantly increased as compared to that in controls (117.5 ± 19.9 vs. 24.2 ± 3.5 cells/mm², P < 0.001). CONCLUSIONS We demonstrate a subclinical involvement in the contralateral clinically unaffected eyes in patients with unilateral acute MK. In vivo confocal microscopy reveals not only a diminishment of the subbasal corneal nerves and sensation, but also an increase in dendritiform cell density in the contralateral unaffected eyes of MK patients. These findings show bilateral immune alterations in a clinically unilateral disease.

Confocal Laser Scanning Tomography to Predict Visual Field Conversion in Patients With Ocular Hypertension and Early Glaucoma.

Purpose:To compare Moorfields regression analysis (MRA), Glaucoma probability score (GPS), and different discriminant functions to predict future visual field conversion of patients with ocular hypertension and early glaucoma. Patients and Methods:The study included 120 eyes of patients with ocular hypertension and 110 eyes of patients with early glaucoma from the Erlangen glaucoma registry. Annually, all patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and HRT (Heidelberg Retina Tomograph I-III; Heidelberg Engineering) measurements. The cohort was divided into 2 groups based on the development of repeatable glaucomatous visual fields. Positive predictive values and negative predictive values were compared for MRA, GPS, and the classification of Bathija, Iester, Mardin, and Mikelberg at baseline. Kaplan-Meier Survival curves and Logrank tests were used to evaluate equality of survival distributions for different test results. Results:Median follow-up was 9.04 years. 26 eyes (11.3%) demonstrated glaucomatous visual field loss in the follow-up. MRA temporal-superior and temporal-inferior outside normal limits were predictive of future visual field loss with positive predictive values of 33.3% and 28.6%. Normal GPS Temporal Sector demonstrated a negative predictive value of 96.4% and normal results in discriminant functions between 94.7% and 95.5%. Conclusions:Confocal scanning laser tomography is a useful imaging modality to predict future visual field conversion. Development of visual field defects in 10 years is highly unlikely, if GPS classification and/or classification of discriminant analysis at baseline are normal. MRA temporal-superior and temporal-inferior outside normal limits are associated with future VF conversion (ClinicalTrials.gov number, NTC00494923).

The Effect of Long-term Antiglaucomatous Drug Administration on Central Corneal Thickness.

Purpose:To evaluate rates of changes per year of central corneal thickness after antiglaucomatous drug administration with &bgr;-blockers, prostaglandin analogs, and carbonic anhydrase inhibitors monotherapy and combined topical antiglaucomatous therapy, in a cohort of patients with ocular hypertension, glaucoma suspects, and patients with perimetric glaucoma as compared with normal controls. Patients and Methods:This retrospective single-center study included 130 eyes as healthy controls, 121 eyes of ocular hypertensive patients, 105 eyes of glaucoma suspects, and 49 eyes of perimetric glaucoma patients. All patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and optical coherence pachymetry (OCP; Heidelberg Engineering). The cohort was divided into 8 groups on the basis of topical antiglaucomatous medication. Linear regression analysis was conducted to analyze the relationship between central corneal thickness and exposure to antiglaucomatous medication during the follow-up. Results:Central corneal thickness did not change during the follow-up for investigated diagnostic subgroups. There was a statistically significant decrease in central corneal thickness for eyes treated with prostaglandin monotherapy (−3.1 &mgr;m/y for left eye), and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and &bgr;-blockers (−5.8 and −3.8 &mgr;m/y for right and left eye, respectively). Conclusions:We recommend regular measurements before and during therapy with prostaglandin monotherapy and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and &bgr;-blockers. Follow-up intraocular pressure measurements may be underestimated for eyes treated with the aforementioned treatment regimens if central corneal thickness is not measured on a regular basis.

Glaucoma diagnostic performance of GDxVCC and spectralis OCT on eyes with atypical retardation pattern.

Purpose:To investigate the impact of typical scan score (TSS) on discriminating glaucomatous and healthy eyes by scanning laser polarimetry and spectral domain optical coherence tomography (SD-OCT) in 32 peripapillary sectors. Patients and Methods:One hundred two glaucoma patients and 32 healthy controls underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, GDxVCC, and SD-OCT measurements. For controls, only very typical scans (TSS=100) were accepted. Glaucoma patients were divided into 3 subgroups (very typical: TSS=100; typical: 99≥TSS≥80, atypical: TSS<80). Receiver operating characteristic curves were constructed for mean retinal nerve fiber layer values, sector data, and nerve fiber indicator (NFI). Sensitivity was estimated at ≥90% specificity to compare the discriminating ability of each imaging modality. Results:For discrimination between healthy and glaucomatous eyes with very typical scans, the NFI and inferior sector analyses 26 to 27 demonstrated the highest sensitivity at ≥90% specificity in GDxVCC and SD-OCT, respectively. For the typical and atypical groups, sensitivity at ≥90% specificity decreased for all 32 peripapillary sectors on an average by 10.9% and 17.9% for GDxVCC and by 4.9% and 0.8% for SD-OCT. For GDxVCC, diagnostic performance of peripapillary sectors decreased with lower TSS, especially in temporosuperior and inferotemporal sectors (sensitivity at ≥90% specificity decreased by 55.3% and by 37.8% in the atypical group). Conclusions:Diagnostic accuracy is comparable for SD-OCT and GDxVCC if typical scans (TSS=100) are investigated. Decreasing TSS is associated with a decrease in diagnostic accuracy for discriminating healthy and glaucomatous eyes by scanning laser polarimetry. NFI is less influenced than the global or sector retinal nerve fiber layer thickness. The TSS score should be included in the standard printout. Diagnostic accuracy of SD-OCT is barely influenced by low TSS.

Atypical retardation patterns in scanning laser polarimetry are associated with low peripapillary choroidal thickness.

PURPOSE Scanning laser polarimetry (SLP) results can be affected by an atypical retardation pattern (ARP). One reason for an ARP is the birefringence of the sclera. The purpose of this study was to investigate the influence of the peripapillary choroidal thickness (pChTh) on the occurrence of ARP. METHODS One hundred ten healthy subjects were investigated with SLP and spectral domain OCT. pChTh was measured in B-scan images at 768 positions using semiautomatic software. Values were averaged to 32 sectors and the total peripapillary mean. Subjects were divided into four groups according to the typical scan score (TSS) provided by the GDxVCC: group 1 TSS, 100; group 2 TSS, 90-99; group 3 TSS, 80-89; group 4 TSS, <80. RESULTS Mean pChTh (± SD) in 110 healthy subjects was 141 μm (±49 μm). There was a significant correlation between pChTh and TSS (r = 0.608; P < 0.001). In TSS groups 1 to 4, mean pChTh was 168 μm (±38 μm), 148 μm (± 48 μm), 119 μm (±35 μm), and 92 (±42 μm). Mean pChTh of TSS groups 3 and 4 was significantly lower than that of TSS group 1 (P < 0.001). CONCLUSIONS Low values of TSS resulting from the appearance of ARP in SLP are associated with low peripapillary choroidal thickness. Reduced choroidal thickness may result in an increased amount of confounding light getting to the SLP light detectors.

Can Glaucomatous Visual Field Progression be Predicted by Structural and Functional Measures

Purpose: The aim of this study was to compare the predictive value of retinal nerve fiber layer thickness (RNFLT) measurements obtained by optical coherence tomography (OCT), morphometric parameters of confocal scanning laser ophthalmoscopy (CSLO), and frequency-doubling technique perimetry to predict visual field conversion of normal individuals, ocular hypertensive subjects, and early preperimetric glaucoma patients as determined by standard automated perimetry (SAP). Patients and Methods: This longitudinal single-center study included 107 eyes of 56 controls, 164 eyes of 98 patients with ocular hypertension, and 169 eyes of 110 patients with preperimetric glaucoma. At baseline, all patients and controls underwent OCT (Spectralis OCT), CSLO (Heidelberg Retina Tomograph) examination, optic disc photography, and frequency-doubling technique perimetry. At baseline SAP was normal in all participants. Univariate and multivariate hazard ratios (HRs) were measured to model the conversion-free survival including morphometric functional and clinical variables. Results: The median follow-up period was 6.9 years. In total, 48 eyes (10.9%) demonstrated visual field conversion in the follow-up. RNFLT temporal-inferior outside normal limits demonstrated the highest HR with 1.2 (95% confidence interval, 1.1-1.4) per 10 &mgr;m loss for OCT, and Glaucoma probability score global outside normal limits demonstrated the highest HR with 1.3 (95 % confidence interval, 1.1-1.5) per 0.1 increase for CSLO in a multivariate model adjusted for photograph-based glaucoma staging, central corneal thickness, and SAP pattern SD. Conclusions: Both measurement of RNFLT by OCT and Glaucoma probability score by CSLO are highly predictive of future visual field conversion and provide independent predictive information beyond optic disc assessment, central corneal thickness, and SAP pattern SD.

Primäres Offenwinkelglaukom – Krankheitsbild und Früherkennung

Das Glaukom, auch Gruner Star genannt, ist weltweit eine der haufigsten irreversiblen Erblindungsursachen. In Deutschland sind Schatzungen zufolge derzeit 950 000 Menschen an Glaukom erkrankt, weltweit 66,8 Millionen, davon 6,8 Millionen an beiden Augen erblindet. In Europa erkranken ca. 2,42% der > 40-Jahrigen. Die Erkrankung verlauft beschwerdefrei und schmerzlos, die Halfte der Betroffenen ahnt nichts von ihrer Erkrankung. Die Anzahl unentdeckter Glaukome ist hoch, da es erst zu Gesichtsfeldausfallen kommt, wenn bereits ein groser Anteil retinaler Ganglienzellen untergegangen ist. Die Gesichtsfeldausfalle beginnen oft an den Randbereichen des Gesichtsfelds, sodass sie uber einen langen Zeitraum nicht bemerkt werden. Viele Patienten werden erst diagnostiziert, wenn bereits ein irreversibler Schaden des Sehnervenkopfes eingetreten ist.