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Thomas Kaercher,1 Elisabeth M Messmer,2,3 Thomas Berninger,4 Klaudia K Huber-van der Velden,5 Raphaela Geiger,6 Pauline Cipriano-Bonvin,7 Christina Jacobi8,9 1Augenarztpraxis, Heidelberg, Germany; 2Department of Ophthalmology, Ludwig-Maximilian-University, Munich, Germany; 3Praxis Professor Kampik & Kollegen, Munich, Germany; 4Augenzentrum, Olching, Germany; 5Augenheilkunde Lindenthal, Köln-Lindenthal, Germany; 6TRB Chemedica AG, Feldkirchen, Germany; 7TRB Chemedica International SA, Geneva, Switzerland; 8Augen & Haut Zentrum-Praxis Dr. Jacobi, Nuremberg, Germany; 9Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, GermanyCorrespondence: Thomas Kaercher, Augenarztpraxis, 48 Dossenheimer Landstr, Heidelberg, 69121, Germany, Tel +49 6221 400 888, Fax +49 6221 412 203, Email thomas.kaercher@meibomius.dePurpose: To investigate the efficacy, safety and tolerability of topical omega-3 polyunsaturated fatty acids (PUFA) as an innovative treatment of dry eye disease (DED).Patients and Methods: In a pilot, multicenter, masked-observer, randomized, active-controlled, non-inferiority study in Germany, patients self-treated their eyes with daily instillations of eye drops containing either omega-3 PUFA or povidone as major components for three months. At four and twelve weeks, efficacy was among others evaluated based on Ocular Surface Disease Index (OSDI), ocular surface symptoms intensity, general clinical impression, tear break-up time (TBUT), corneal fluorescein staining using the Oxford grading scale, tear volume, and matrix metalloproteinase-9 (MMP-9) concentration in the tear film. Safety evaluation included visual acuity, intraocular pressure, and the incidence of adverse events. Co-primary endpoints were the mean percent changes from baseline of TBUT and OSDI after four weeks.Results: In total 80 patients were included, of whom 37 in the PUFA group and 39 in the povidone group were evaluable for the co-primary endpoints. Patients had a mean age of 52 years and > 80% were women. Both co-primary endpoints (TBUT and OSDI) significantly improved from baseline in both treatment groups, at Week 4 and Week 12 and the statistical analysis demonstrated topical omega-3 PUFA to be non-inferior to 2% povidone for these two parameters. Both treatments resulted in a significant improvement of most secondary efficacy endpoints as well, often with a slight difference in favor of PUFA, not reaching statistical significance though. One non-severe, treatment-related local AE was reported in each group.Conclusion: Omega-3 PUFA-based eye drops proved to be non-inferior to povidone-containing eye drops in the treatment of signs and symptoms of dry eye. This treatment may thus be an additional tool for the management of DED.Keywords: polyunsaturated fatty acids, povidone, dry eye disease, artificial tears, omega-3 fatty acid

Ziel ist es, die im SLO-mfERG objektiv nachweisbaren retinalen Funktionsminderungen mit den in der Mikroperimetrie unter Anwendung unterschiedlicher Stimulusintensitaten messbaren Skotome in Vergleich zu setzen. Bei 4 Patienten mit Morbus Stargardt wurden ein SLO-mfERG und eine SLO-Mikroperimetrie durchgefuhrt. Das SLO-mfERG wurde in einem Messfeld von 24° Durchmesser am hinteren Augenpol unter simultaner Fixationskontrolle abgeleitet. Die Stimulation erfolgte mit einem Helium-Neon-Laser, die Darstellung des Augenhintergrundes mit einem Infrarotlaser. Die SLO-Mikroperimetrie wurde mit einem Stimulus, dessen Winkelgrose dem Goldmann-III-Stimulus entspricht, bei Intensitaten von 0 dB, 12 dB und 20 dB durchgefuhrt. Es wurde die Amplitudenreduktion im SLO-mfERG mit der Skotomgrose bei verschiedenen Stimulusintensitaten in der SLO-Mikroperimetrie korreliert. Die in der SLO-mfERG Untersuchung topographisch zuordenbaren Funktionsminderungen zeigten eine enge Ubereinstimmung mit der Grose der Skotome in der SLO-Mikroperimetrie bei Anwendung der Kombination Prufmarke Goldmann III/20dB. Sowohl das SLO-mfERG als auch die SLO-Mikroperimetrie stellen eine sensitive Untersuchungstechnik zur Quantifizierung retinaler Funktionsdefizite dar und eignen sich zur Durchfuhrung einer detaillierten Netzhautfunktionsdiagnostik.

Purpose To demonstrate the possibility of topographic mapping of retinal function under simultaneous control of fixation in humans, by scanning laser ophthalmoscope evoked multifocal electroretinography (SLO-m-ERG). Methods A confocal scanning laser ophthalmoscope was used as a stimulator and trigger unit to take m-ERGs. Short m-sequences based on a modified algorithm were used, with the advantage that each measurement cycle can be evaluated separately. We examined 78 normal subjects; in 62 a distortion factor of 1:1 was applied, and a factor of 1:4 in 16. Results The recorded amplitudes decreased with eccentricity, approximately following the decrease of retinal cone density. Amplitudes were higher in the central hexagonal element in the group with 1:4 distortion than in the group with the 1:1 distortion setting. Conclusions SLO-m-ERG is a reliable technique for topographic mapping of retinal function under simultaneous control of fixation

Background: Mutations in the OA1 gene on the short arm of the X chromosome are known to cause X-linked ocular albinism (xlOA) in males. A four-generation family with this disorder, including asymptomatic carrier females, was investigated by molecular analysis of the OA1 gene. Methods: DNA samples were available from 22 individuals of this family, including 6 affected males and 6 obligate carriers. The nine exons of the OA1 gene were amplified and further analyzed by SSCP and sequencing. Results: A detailed clinical examination of the index patient and two female carriers showed the typical signs of ocular albinism. Visual evoked potential responses showed markedly asymmetrical responses from the two hemispheres in the affected person as well as in the carriers, as a result of misrouting and decussation of optic nerve fibers. Molecular genetic analysis demonstrated a previously undescribed 29-bp deletion at position 225–253 in exon 1 of the OA1 gene, which segregated in the family. Conclusion: Clinical examination combined with molecular genetic analysis enhances the potential for a precise diagnosis for persons at risk of xlOA and provide an accurate basis for genetic counseling.

Background It is difficult to quantify thresholds in most colour vision tests, and this is especially the case for tritan hues, where a strong age-related increase of threshold has been reported. With the development of computer-graphic methods it is possible to remove brightness clues caused by lens absorption. This study attempts to give normative values for colour contrast thresholds and assess the age related changes therein. Patients and methods 11 5 patients aged between 6 & 71 years were tested for central and peripheral colour contrast sensitivity. s No patient had any systemic or eye disease. As a preliminary, heterochromatic flicker balance between the luminosities of the R and G and B and G phosphors was established, so that all colours subsequently generated were isoluminant for the person tested. Then, using a modified binary search technique, t colour contrast thresholds were established using both 2 degree optotypes, for central vision, and a ring, 12.5 degrees in radius t for peripheral vision. In the latter case, the observer had to name the position of the missing quadrant in the ring. Stimuli were presented for 200 msec at 1 Hz. Colours were modulated on protan, deutan or tritan colour axis. Results No correlation between age and central colour vision thresholds was observed. By contrast a significant but only minor increase of peripheral colour vision threshold was observed for the peripheral protan and tritan axis. Discussion The present system removes luminance clues from colour vision tests and permits both central and peripheral retina to be tested. The results are simple in that the influence of age can be neglected. The variability of threshold results is small, and it is easy to detect the relatively large changes associated with disease. Since high-quality monitors are standardised and calibrated, providing the stimulus parameters described are adhered to, the results given here for upper limits of normal may be used for other similar systems.

A significant difference in the response density of the MF-ERG response has been suggested for every 2 diopter change of refraction. The influence of refractive blur on the MF-ERG was studied in 8 healthy volunteers using either the VERIS™ system (Group A: n=5) or Retiscan™ (Group B: n=3). For each eye recordings were obtained with a corrective lens of −3 dpt, 0 dpt, +3 dpt and +6 dpt placed in front of the contact lens electrode. The viewing distance was adjusted to compensate for the induced changes in the retinal image size. When the changes in retinal image size due to the refractive lens were compensated for, no influence due to refraction was observed in either latencies or amplitudes of (KI (P>0.05). This held true for the central response average (four degrees) as well as for the outer 6–25 degrees. In KII.1 only the peripheral amplitudes of Group B showed an influence due to refraction (P≤0.05). This may be due to adaptation as the recordings of group B were obtained in succession. As expected, significant differences were observed when the recordings obtained with the different systems were compared (P≤0.05).

Color vision tests were performed on 211 German ophthalmologists during their annual meeting at Essen. The subjects also answered detailed questionnaires about their use of lasers and operating microscopes, and their ocular and general health. It was found that 33% of doctors who use lasers or operating microscopes have decreased color discrimination for colors in a tritan color-confusion axis (>2 standard deviations above normal). There is a relationship between number of patients treated and the degree of threshold elevation. Thirty hours of using the operating microscope produces an increase in tritan threshold equivalent to one panretinal photocoagulation.

Background: The pattern ERG can be used to detect early glaucomatous change, because the response of cells in the inner retina from (typically) 20°–40° of area is reduced before perimetric abnormality is certain. The multifocal pattern electroretinogram (mfPERG) allows analysis of many local regions within this area. The aim of this study was to investigate whether in patients with presumed glaucoma the mfPERG permits diagnosis and discrimination from normals. Methods: Measurements on 25 age-related normal eyes were compared to those on 23 eyes with different stages of glaucoma. A RETIScan system was used to generate a stimulus pattern of 19 hexagons, each consisting of six triangles. The triangles pattern-reversed black to white at 75 Hz. Those 19 hexagons were grouped into three stimulus regions: a central field, a middle, and a peripheral ring. The complete array subtended 48° at the eye. The hexagons alternated between black and white, in a temporal pattern that followed a corrected binary m-sequence (length 512, 10 cycles with 39 s each). The amplitudes and latencies of positive responses at approximately 50 ms (P-50) and negative responses at approximately 95 ms (N-95) were analyzed. Results: In patients with glaucoma the P-50 and N-95 components of the mfPERG were significantly reduced for the central area and both outer rings compared to normal volunteers (p

Purpose: Optimal screening for ocular toxicity caused by chloroquine and hydroxychloroquine is still controversial. With the multifocal pattern electroretinogram (mfPERG), a new electrophysiological technique has recently become available to detect early changes of ganglion cells. In this study this new technique is applied to a series of 10 patients seen consecutively receiving long-term chloroquine medication. Methods: In 10 patients receiving chloroquine medication, clinical examination, Amsler visual field testing and computerized color vision testing were performed. If toxicity was suspected, automated perimetry was carried out. In addition, in all patients conventional pattern electroretinogram (PERG) and mfPERG testing were performed. Results: On clinical examination 8 patients showed no chloroquine-associated maculopathy, while 2 patients did. Of these 2, only 1 reported abnormalities when viewing the Amsler chart, while automated perimetry showed typical, ring-like paracentral scotomas in both affected patients and color vision was significantly abnormal. In the normal patients, 4 of 8 had a mild color vision disturbance, which correlated to age-related macular changes. The amplitudes of the PERG and the central (approximately 10°) responses of the mfPERG were markedly reduced in chloroquine maculopathy, while the latencies were unchanged. The peripheral rings of mfPERG (ranging to 48°) were not affected by chloroquine toxicity. Both PERG and mfPERG were less affected by age-related macular changes. Conclusions: The reduction of PERG and central mfPERG responses in chloroquine maculopathy may help with the early detection of toxicity.

Purpose: to measure changes in the relative spectral sensitivities of the dark adapted and light adapted ERG and thus to establish the possible contribution of rods to the ‘blue cone’ ERG elicited by flashes of blue light. Background: short wavelength stimuli in the light-adapted eye evoke small rounded b-waves which have been considered to be S-cone responses. We have recorded such responses from tritanopes, which called the assumptions into question. Methods: small ERGs were recorded to blue and green flashes. The stimulus was a Ganzfeld which employed light emitting diodes. ERGs were obtained in both the dark-adapted eye and after light adaptation to intense orange light (peak wavelength 610 nm). The change in sensitivity with light adaptation and the relative spectral sensitivity was determined from the voltage/log light intensity functions, using a 10 μV criterion. Results: (1) peak times and changes in sensitivity did not help distinguish light-adapted rod from possible S-cone responses; (2) analysis of the change in the ratio of blue:green sensitivity from darkness to 4.4 log Td. 610 nm background suggests that in seven normal subjects, 90% or more of the ERG evoked by 440 nm flashes is generated by S-cones; (3) three tritanopes have insignificantly reduced S-cone responses. Conclusions: (1) clinical techniques used to isolate S-cone ERGs are appropriate; (2) there are at least two types of tritanope and in those we investigated, functional S-cones are probably displaced into the retinal periphery.

Retinitis pigmentosa (RP) is a genetically heterogeneous group of progressive hereditary retinal dystrophies. All three modes of Mendelian inheritance, autosomal dominant, autosomal recessive, and X-linked have been described. Even within the same mode of inheritance further genetic heterogeneity has been proven during the last three years as different genes/loci on different chromosomes have been identified for autosomal dominant retinitis pigmentosa (adRP) (for review see ref.1, and Farrar et al., this volume). The gene for rhodopsin which is localized on the long arm of chromosome 3 was the first adRP gene identified2. Since then an ever increasing number of allelic rhodopsin mutations have been described3. Different types and methods of subgrouping of adRP had been suggested on the basis of clinical observations4–8. The most widely accepted classification is that of Massof and Finkelstein who divided adRP in two types5. Type I is characterized with a diffuse loss of rod function and with an onset of night blindness usually during the first decade of life. The cone function is relatively well preserved throughout life. In contrast, type II (“sector”) of adRP shows a regional loss of both rod and cone function, and a much later onset of night blindness. Type I is identical to type “D”, and type II to type “R” according to Lyness and coworkers8. As this classification is based solely on phenotypic features, identification of the primary genetic defect may allow a more appropriate subtyping.