Combined cSLO-OCT imaging as a tool in preclinical ocular toxicity testing: A comparison to standard in-vivo and pathology methods.

INTRODUCTION: Confocal scanning laser ophthalmoscopy and optical coherence tomography (cSLO-OCT) became available for human and animal ophthalmic examinations in recent years. The purpose of this study was to evaluate lesion detection and localization with cSLO-OCT imaging in an experimental outer retinal toxicity model and to compare cSLO-OCT to standard examination methods (indirect ophthalmoscopy (IO), fundus photography (FP) and central section histopathology). METHODS: A test compound was orally administered to albino rats (n = 4) for four weeks (part A) and to albino (n = 2) and pigmented (n = 2) rats for eight weeks (part B). Control animals received vehicle only. Retinal changes were documented using cSLO-OCT, IO, FP, angiography and histopathology. Retinal thicknesses were compared between groups using a mixed effects model. RESULTS: All compound-treated animals developed progressive multifocal hyperreflective spot changes mostly confined to the retinal pigment epithelium. In study parts A and B, cSLO identified fundus lesions earlier than IO/FP in albino rats. In study part B, cSLO quantified fundus lesions more accurately than IO/FP in albino rats but no difference was seen in pigmented rats. Central section histopathology revealed no abnormalities in three out of four compound-treated animals in part B. Altogether, without cSLO-OCT, present fundus changes would have remained undetected in one of four compound-treated animals in both parts A and B. DISCUSSION: Integration of combined cSLO-OCT imaging into toxicology study design can improve toxicity study readouts and facilitate longitudinal examination of single animals at multiple time points, leading to a reduction of experimental animal numbers.

[Diagnostic Precision of the Confocal Scanning Laser Ophthalmoscopy in the Large Optic Disc with Physiological Excavation - a Long-Term Study]. / Diagnostische Zuverlässigkeit der konfokalen Scanning-Laser-Ophthalmoskopie bei großen Papillen mit physiologischer Exkavation ­ eine Langzeitstudie.

We repeatedly examined 17 subjects with presumed bilateral physiological excavation labeled as pathological and/or borderline via HRT to verify the diagnosis of physiological cupping or to monitor the long-term progression into normal tension glaucoma. PATIENTS AND METHODS: 17 Subjects with presumed bilateral physiological cupping and large optic discs were included in this long-term follow-up study. All subjects underwent regular detailed ophthalmologic examinations, including intraocular pressure measurement via Goldmann applanation tonometry (GAT), retinal nerve fiber layer imaging via optical coherence tonometry (OCT) and visual field testing and optic disc imaging using the HRT. Glaucomatous progression was identified using the HRT's tools (stereometric trend analysis [STA] and topographic change analysis [TCA]). RESULTS: In the initial examination, all 17 subjects were classified as "pathological", by the HRT's Moorfield's Regression Analysis (MRA). Over the observation period of 9.2 ± 5 years, only 1 of the 17 subjects showed an ensured conversion to normal tension glaucoma with glaucomatous visual field defects. The remaining 16 subjects show no visual field defects to date. STA showed significant changes in 3 subjects alone, in 1 subject TCA showed a significant change alone, and in 1 subject both analyses showed a progressive change. CONCLUSION: After 9 years of regular examinations, 16 of the 17 subjects that were classified as "pathological" using MRA showed no glaucomatous visual field defects. In 5 out of these 16 subjects, progressive changes of the optic disc could be recorded via HRT. Therefore, the diagnostic precision of the HRT measurements seems to be limited in patients with large discs and physiological cupping.

Glaucoma.

Glaucoma is a heterogeneous group of diseases characterised by cupping of the optic nerve head and visual-field damage. It is the most frequent cause of irreversible blindness worldwide. Progression usually stops if the intraocular pressure is lowered by 30-50% from baseline. Its worldwide age-standardised prevalence in the population aged 40 years or older is about 3·5%. Chronic forms of glaucoma are painless and symptomatic visual-field defects occur late. Early detection by ophthalmological examination is mandatory. Risk factors for primary open-angle glaucoma-the most common form of glaucoma-include older age, elevated intraocular pressure, sub-Saharan African ethnic origin, positive family history, and high myopia. Older age, hyperopia, and east Asian ethnic origin are the main risk factors for primary angle-closure glaucoma. Glaucoma is diagnosed using ophthalmoscopy, tonometry, and perimetry. Treatment to lower intraocular pressure is based on topical drugs, laser therapy, and surgical intervention if other therapeutic modalities fail to prevent progression.

Evaluating outer segment length as a surrogate measure of peak foveal cone density.

Adaptive optics (AO) imaging tools enable direct visualization of the cone photoreceptor mosaic, which facilitates quantitative measurements such as cone density. However, in many individuals, low image quality or excessive eye movements precludes making such measures. As foveal cone specialization is associated with both increased density and outer segment (OS) elongation, we sought to examine whether OS length could be used as a surrogate measure of foveal cone density. The retinas of 43 subjects (23 normal and 20 albinism; aged 6-67years) were examined. Peak foveal cone density was measured using confocal adaptive optics scanning light ophthalmoscopy (AOSLO), and OS length was measured using optical coherence tomography (OCT) and longitudinal reflectivity profile-based approach. Peak cone density ranged from 29,200 to 214,000cones/mm2 (111,700±46,300cones/mm2); OS length ranged from 26.3 to 54.5µm (40.5±7.7µm). Density was significantly correlated with OS length in albinism (p<0.0001), but not normals (p=0.99). A cubic model of density as a function of OS length was created based on histology and optimized to fit the albinism data. The model includes triangular cone packing, a cylindrical OS with a fixed volume of 136.6µm3, and a ratio of OS to inner segment width that increased linearly with increasing OS length (R2=0.72). Normal subjects showed no apparent relationship between cone density and OS length. In the absence of adequate AOSLO imagery, OS length may be used to estimate cone density in patients with albinism. Whether this relationship exists in other patient populations with foveal hypoplasia (e.g., premature birth, aniridia, isolated foveal hypoplasia) remains to be seen.

[The efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in retinoblastoma therapy].

Objective: To evaluate the efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in the treatment of early and middle stage retinoblastoma. Methods: Retrospective series case study. Clinical data of 21 patients (22 eyes) who were diagnosed as retinoblastoma (RB) in Peking University People's Hospital from March 2009 to August 2014 were collected. Medical and family history, ocular ultrasound, orbital and cranial MRI or CT examination of RB Children were detailed recorded. Ocular examination and laser treatment were performed under general anesthesia, once every 3-4 weeks until the tumor was under control. The observation period was at least 3 months after the last treatment. The ocular examination included intraocular pressure measurement, anterior segment and fundus examination and the fundus photography with Retcam. Laser therapeutic instrument was large spot indirect ophthalmoscopy laser of 810nm wavelength. Results: Of the 21 children, 16 were male and 5 were female. The range of age was 3 to 82 months averaged 17.3 months. Among 22 eyes, four with small tumor, eight with medium tumor, and ten with large tumor. Two eyes underwent laser treatment only and 20 eyes underwent laser treatment combined with systemic chemotherapy. During the average observation period of 33.9 months, 15 tumors were treated successfully, but 7 failed. The total success rate was 68.2%. The number and success rate of small, medium and large tumor eyes were 4 (100%), 5 (62.5%) and 5 (50%), respectively. There was one case of tumor brain metastases, and the classification of contralateral eye of the child was E phase. COMPLICATIONS: Iris burns happened in one eye, obvious vitreous proliferation in one eye and mild vitreous hemorrhage occurred in two eyes, which did not affect the treatment of laser. However, obvious tumor hemorrhage happened in two eyes and affected laser therapy. There was no complicated cataract, iatrogenic retinal hole and tumor intravitreal implant caused by laser blasting effect. Conclusions: Indirect ophthalmoscope laser in 810-nm diode laser with large-spot alone or combined with systemic chemotherapy may be effective treatment for retinoblastoma in earlier than stage C of international classification. It is suitable for large and multiple retinoblastoma.(Chin J Ophthalmol, 2016, 52: 745-748).

Green tea catechins are potent anti-oxidants that ameliorate sodium iodate-induced retinal degeneration in rats.

Green tea extracts exhibit anti-oxidative and anti-inflammatory actions in different disease conditions. We hypothesized that green tea extract and its catechin constituents ameliorate sodium iodate-induced retinal degeneration in rats by counteracting oxidative stress. In this study, adult Sprague-Dawley rats were intravenously injected with a single dose of sodium iodate. Green tea extract (GTE; Theaphenon-E) or combinations of its catechin constituents, including (-)-epigallocatechin gallate (EGCG), were administered intra-gastrically before injection. Live imaging analysis using confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography showed a progressive increase of degenerating profile across the retinal surface and decrease in thickness of outer nuclear layer (ONL) at Day-14 of post-injection. These lesions were significantly ameliorated by Theaphenon-E and catechin combinations with EGCG. Catechins with exclusion of EGCG did not show obvious protective effect. Histological analyses confirmed that Theaphenon-E and catechins containing EGCG protect the retina by reducing ONL disruption. Retinal protective effects were associated with reduced expression of superoxide dismutase, glutathione peroxidase and caspase-3, and suppression of 8-iso-Prostaglandin F2α generation in the retina. In summary, GTE and its catechin constituents are potent anti-oxidants that offer neuroprotection to the outer retinal degeneration after sodium iodate insult, among which EGCG is the most active constituent.

[Specifity of optic disc evaluation in healthy subjects with large optic discs and physiologic cupping using confocal scanning laser ophthalmoscopy]. / Spezifität der konfokalen Scanning Laser Ophthalmoskopie bei großen Sehnerven mit physiologischer Exkavation.

PURPOSE: Imaging methods of the optic nerve head appear to have an increasing impact in glaucoma diagnosis. The aim of this study is to evaluate the specifity of the Heidelberg Retina Tomograph (software version 1.7 and 3.0) in subjects with physiological cupping and large optic discs. PATIENTS AND METHODS: 27 eyes of 27 subjects (mean age 41.3 ± 15.8 years) with bilateral physiological cupping and large optic discs (vertical cup-to-disc-ratio > 0.3, optic disc area 2.48 ± 0.45 mm2, max. 3.54 mm2) were included in a clinical study. All subjects had an intraocular pressure < 22 mmHg, physiological cupping by funduscopy and no nerve fibre layer defects (Scanning Laser Ophthalmoscope, Rodenstock, Germany). Standard achromatic perimetry (Humphrey Field Analyzer, Humphrey-Zeiss, 24/2 SITA or full threshold), short-wavelength automated perimetry (Humphrey Field Analyzer, Humphrey-Zeiss), and frequency doubling technology (FDT, Humphrey-Zeiss) revealed no visual field defects. Optic disc imaging was performed in all subjects using the Heidelberg Retina Tomograph II (HRT). Optic disc images were transferred to the software-update of the HRT 3 (Version 3.0, Heidelberg Engineering). Specifity was calculated using the Moorfields regression analysis (MRA, software version 1.7 and 3.0) and the glaucoma probability score (GPS analysis) using all disc sectors and omitting the nasal and 3 nasal sectors. RESULTS: Specifity of the MRA (software version 1.7) was 66.6 % (most specific criteria), and 22.2 % (least specific criteria). Specifity of the MRA (software version 3.0) was 33.3 % (most specific criteria), and 14.8 % (least specific criteria), whereas specifity of the GPS analysis was 37.0 % (most specific criteria), and 11.1 % (least specific criteria). When the nasal sectors were omitted for analysis, specifity increased for the MRA analysis, but not for the GPS analysis. CONCLUSIONS: Specifity of the MRA was unsatisfactory using the software version 1.7 and 3.0 in subjects with large optic discs and physiological cupping when the nasal sectors were included in the analysis. The observer-independent GPS analysis did not improve the results in these subjects.

Rose bengal staining as an assessment of ocular surface damage and recovery in dry eye disease-a review.

PURPOSE: To review the use of ophthalmic rose bengal to assess the ocular surface, especially considering the grading scales used. METHODS: A literature search was undertaken to identify reports where either rose bengal or lissamine green had been used as a 'vital' stain, with a special interest in identifying studies that provided data before and after treatment for dry eye and also considered the mechanism of action of these two chemicals. RESULTS: Between 1985 and 2006, numerous clinical studies used a consistent grading scheme (that attributed to Van Bijsterveld) to assess the outcome of artificial tear treatments on dry eye patients. With such consistency, including the adoption of a treatment period of 1 month, comparisons can be made to indicate the efficacy of rose bengal staining to assess reduction in ocular surface desiccation. However, in the following years, several alternative grading schemes have been used for both rose bengal and lissamine green and assessment periods have been variable so making inter-study comparisons considerably more difficult to undertake. An attribute of rose bengal appears to be its ability to stain the nuclei of cells, but whether this also occurs for lissamine green is unclear. CONCLUSIONS: Ophthalmic rose bengal has been successfully adopted for use to assess the ocular surface over many years as a vital stain. More research is needed to assess whether lissamine green ocular surface staining can simply be substituted for rose bengal in evaluation of dry eye treatments.

[Screening ROP in the University Hospital Ostrava]. / Screening ROP ve FN Ostrava.

OBJECTIVE: To analyze the group of premature infants who were examined by an ophthalmologist in screening for ROP (retinopathy of prematurity) at the University Hospital in Ostrava. METHODS: A retrospective observational case series. We reviewed and analyzed clinical records of all the premature infants born before the 32nd gestational week examined by ophthalmologist in ROP screening at the University Hospital in Ostrava in the period from 1. 9. 2011 to 31. 8. 2012. Childrens gestational age at birth, birth weight, postconceptional age (PCA) of the child at the time of the first ocular inspection, at the time of diagnosis ROP and at the time of any intervention, possible risk factors of ROP (Apgar score in the 1st minute, duration of oxygen therapy, FiO2 (%) (percentage fraction of oxygen in the inspired gas mixture), duration of mechanical ventilation, transfusion of erythrocytes (resuspended leukodepleted), presence of sepsis / infection in the perinatal period and duration of phototherapy) were evaluated. Eye examination was performed in local anesthesia with the use of an eyelid retractor, in artificial mydriasis, using an indirect ophthalmoscope and digital imaging system RetCam 3. RESULTS: 138 premature infants with an average gestational age at birth of 29.8 weeks, average birth weight 1385 g, were included in this study. Thirty-four children (24.6 %) were diagnosed with ROP, in all cases 1st stage at the time of diagnosis. An ophthalmologist indicated and subsequently implemented intervention (cryotherapy / laser treatment) in the case of five children (14.7 %) with ROP under general anesthesia. Average duration of oxygen therapy at infants with ROP was 371 hours, in the group without ROP 84 hours. The difference between the average values was statistically significant [t (37) = -3.69, P <= 0.0007]. Average time of mechanical ventilation in the case of children with ROP were 229 hours, in the group without ROP 41 hours [t (35) = -2.99, P <0.005]. In the case of children with ROP, we noticed on average 3 transfusions of erythrocytes, in the group without ROP 1 transfusion [t (40) = -3.94, P <= 0.0003]. The average value of the Apgar score in the 1st minute of children with ROP group was 6.3 and children without ROP 7.8. The difference between the average values of Apgar score in the 1st minute was between both groups statistically significant [t (136) = 4.06, P <= 0.00008]. Sepsis / infection in the perinatal period occurred in 30 (88.2 %) children with ROP, in comparison with 46 (44.2 %) children with sepsis / infection without ROP. Average duration of phototherapy in infants with ROP was 42.4 hours, in the group without ROP 53.6 hours [t(136) = 1,21, P<= 0,2]. CONCLUSION: This study demonstrated statistically significant correlation of Apgar score in the 1st minute, duration of oxygen therapy, duration of mechanical ventilation, transfusion of erythrocytes and presence of sepsis / infection on the onset and progression of ROP at premature infants in our group. No effect of FiO2 (%) and duration of phototherapy on the onset and progression of ROP was demonstrated.

Optic disc morphology in premature infants.

BACKGROUND: To date, little is known about the morphology of optic discs in premature infants. However, optic disc morphology and optic nerve development are two factors that potentially influence visual function in infants. Thus we analysed the morphology of the optic disc and its correlation with gestational age and birth weight. METHODS: In a retrospective trial, we assessed the widefield images (RetCam system) of 111 optic discs of 61 premature infants. We evaluated the form of the optic disc, defined by the ratio of the vertical to the horizontal diameter, the presence or absence of visible disc cupping, the cup to disc ratio and the presence or absence of a double ring (a concentric paler zone around the optic disc). RESULTS: 110 of 111 optic discs had a vertical-oval form. We found a significant negative correlation between the form of the optic disc and birth weight (p=0.003) and gestational age (p=0.03); 75% of optic discs showed a double ring and 89% had visible disc cupping. CONCLUSIONS: In our study, premature birth was associated with the presence of a double ring. A low birth weight and low gestational age influence the form of the optic disc.

[Selected aspects of pediatric ophthalmology for non-pediatric ophthalmologists. Part 2: The odd looking optic nerve head in infants]. / Ausgewählte Aspekte der Kinderophthalmologie für Nicht-Kinderophthalmologen. Teil 2: Die "merkwürdig" aussehende Papille beim Kleinkind.

This article describes the clinical presentation of the most common congenital optic disc findings: optic nerve hypoplasia, optic disc cupping and pediatric optic atrophy. Particular emphasis is placed on the often difficult question: is it a physiological variant or is it pathological? Do I need further investigations? Pragmatic clinical hints are given to enable ophthalmologists to recognize normal variants with greater certainty but also not to overlook congenital optic nerve pathologies. Congenital anomalies of the optic nerve (head) are more common than half a century ago. They can affect the visual development and thus the general infantile development to a large extent if presenting bilaterally. They can occur isolated, with other ocular pathologies and/or accompanied by systemic diseases or syndromes, such as septo-optic dysplasia, albinism, prematurity, small for gestational age birth, as well as due to toxic exposure during pregnancy (e.g. drugs, alcohol and maternal diabetes). In addition to clinical illustrations to distinguish between physiological variants and pathologies of the optic nerve head, the different diagnostic and therapeutic options depending on the age of presentation of the infant are outlined. The reader will obtain some guidelines for distinguishing congenital and acquired optic nerve pathologies. The focal point of the present paper is with infants aged 0-2 years where many diagnostic imaging and psychophysical techniques cannot be applied. Therefore, this age group is the most difficult to correctly discriminate between physiological and pathological findings and to decide whether further diagnostic and/or treatment steps are necessary.

An assessment of the ocular safety of excipient maleic acid following intravitreal injection in rabbits.

Maleic acid was formulated in 0.7% saline and injected intravitreally in rabbits in order to evaluate ocular safety and tolerability. Maleic acid was formulated within a narrow pH range (2-3), administered in a fixed volume (100 µl), and concentrations ranged from 0.00 to 2.00 mg/eye (0.00 to 12.30 mM vitreous). Ocular evaluations were conducted at 2, 4, and 8 days post injection. Ocular irritation responses were observed at doses from 0.50 mg/eye (3.07 mM vitreous) to 2.00 mg/eye (12.30 mM vitreous) and included conjunctival redness and scleral swelling. Chemosis was observed at 2.00 mg/eye (12.30 mM vitreous). Funduscopic evaluations revealed enlarged retinal blood vessels and optic disk swelling at doses ≥1.50 mg/eye (9.22 mM vitreous), retinal folds and retinal discoloration at 2.00 mg/eye (12.30 mM vitreous). Histopathologic evaluations on days 4 and 8 post injection revealed retinal degeneration at doses ≥1.0 mg/eye (6.15 mM vitreous), conjunctival inflammation at doses ≥1.5 mg/eye (9.22 mM vitreous), and retinal pigment epithelial hypertrophy, optic nerve demyelination, anterior chamber fluid, and conjunctival fibrosis at 2.00 mg/eye (12.30 mM vitreous) maleic acid. The data suggest that maleic acid formulations at ≥1.00 mg/eye (6.15 mM vitreous) were not suitable for intraocular indications.

Low-level laser therapy improves visual acuity in adolescent and adult patients with amblyopia.

OBJECTIVE: The purpose of this study was to examine the effects of low-level laser therapy (LLLT) on visual acuity in adolescent and adult patients with amblyopia. BACKGROUND DATA: Currently, amblyopia can be treated successfully only in children. METHODS: In this single-blinded, placebo-controlled study, 178 patients (mean age 46.8 years) with amblyopia caused by ametropia (110 eyes) or strabismus (121 eyes) were included. For LLLT, the area of the macula was irradiated through the conjunctiva from 1 cm distance for 30 sec with laser light (780 nm, 292 Hz, 1:1 duty cycle; average power 7.5 mW; spot area 3 mm(2)). The treatment was repeated on average 3.5 times, resulting in a mean total dose of 0.77 J/cm(2). No occlusion was applied, and no additional medication was administered. Best corrected distant visual acuity was determined using Snellen projection optotypes. In 12 patients (12 eyes), the multifocal visual evoked potential (M-VEP) was recorded. A control group of 20 patients (20 eyes) received mock treatment. RESULTS: Visual acuity improved in ∼90% of the eyes treated with LLLT (p<0.001), increasing by three or more lines in 56.2% and 53.6% of the eyes with amblyopia caused by ametropia and strabismus, respectively. The treatment effect was maintained for at least 6 months. The mean M-VEP amplitude increased by 1207 nV (p<0.001) and mean latency was reduced by 7 msec (p=0.14). No changes were noted in the control group. CONCLUSIONS: LLLT led to a significant improvement in visual acuity in adolescent and adult patients with amblyopia caused by ametropia or strabismus.

[Complex diagnosis of the early macular changes due to AMD]. / Kompleksowa diagnostyka wczesnych zmian w plamce w przebiegu zwyrodnienia plamki zwiazanego z wiekiem.

We demonstrated diagnostic cases of the early macular changes due to AMD, which caused central visual field disturbances. The aim of the study was to systemize the management in patients with macular lesions due to the age related macular degeneration, frequency determination and statement of the performed additional tests range. Patients reported central visual field distortions. We performed visual acuity testing, stereoscopic eye fundus examination, and PHP (macular visual field testing), which objectified distortions symptoms. Based on that tests and fellow eye condition, decision about OCT and FA and ICG performance were made. Further management was determined according to the results of that examinations: follow-up with vitamins and microelements supplementation or PDT. Our analysis confirm, that to monitor early macular changes due to AMD, follow-up examinations in 2-3 months interval are indicated: visual acuity testing, stereoscopic eye fundus examination and macular lesions modeling in PHP In difficult cases or in more advanced lesions FA, OCT and ICG were performed.

Cup-to-disc ratio: agreement between slit-lamp indirect ophthalmoscopic estimation and stratus optical coherence tomography measurement.

PURPOSE: To determine agreement between slit-lamp indirect ophthalmoscopy and Stratus optical coherence tomography (OCT) when assessing cup-to-disc ratios (CDRs). METHODS: Twenty-five ocular hypertensive subjects and 56 patients with primary open-angle glaucoma were included. Estimation of vertical (VCDR) and horizontal (HCDR) cup-to-disc ratio with slit-lamp ophthalmoscopy was made by three glaucoma specialists along with OCT scanning of optic nerve head. Agreement between OCT and specialists was measured by intraclass correlation coefficients (ICC), Bland and Altman's scatterplots, and a regression coefficient of the average difference. RESULTS: The mean VCDR and HCDR was significantly higher (P<0.001) with OCT than that estimated by the specialists, with the difference ranging from 0.08 to 0.11, and from 0.13 to 0.18, respectively, depending on the specialist. Difference was higher (P<0.001) for cuppings below 0.3, and looses significance for larger VCDR cuppings (above 0.7). ICC for VCDR was 0.87 among specialists, and ranges from 0.82 to 0.75 when comparing OCT and specialists. ICC for HCDR was 0.83 among specialists and 0.74 between OCT and specialists. When data were plotted according to the Bland-Altman method, as the cupping increased, the agreement also increased. CONCLUSIONS: There is very good agreement among the specialists when estimating CDRs by stereoscopic slit-lamp biomicroscopy. OCT shows higher values than the specialists; the greatest differences occurred when assessing small CDRs and the differences diminished as the cupping increased. These two methods of measurement are not interchangeable, and the difference must be considered, especially in discs with smaller CDRs.

[Fundus spectrometry in age-related maculopathy]. / Fundusspektrometrie bei altersbezogener Makulopathie.

BACKGROUND: Spectroscopic methods permit the non-invasive detection of fundus pigments by the wavelength-dependent absorption of fluorescence as well as by the fluorescence lifetime. From the relative concentrations of haemoglobin and oxyhaemoglobin, the oxygen saturation can be calculated. The onset of age-related maculopathy might be delayed by a high optical density of xanthophyll. The detection of alterations in fundus autofluorescence points to age-related pathomechanisms (accumulation of lipofuscin, formation of connective tissue). The detection of autofluorescence of redox-pairs of coenzymes results in information about metabolic states at the cellular level, and might make possible an early detection of age-related changes when they are still reversible. METHOD: The evaluation of reflectance spectra, detected by imaging ophthalmo-spectrometry, results in the calculation of oxygen saturation or in the optical density of xanthophyll or of melanin. Fluorescence spectra can be measured also by this technique. For the 2-dimensional determination of the distribution of xanthophyll, a very simple method was developed, requiring fundus illumination by one wavelength only. In the detection of time-resolved autofluorescence, the fluorescence lifetime is used for the determination of endogenous fluorophores. RESULTS: As result of comparing studies between ARM patients and healthy subjects, the consumption of retinal oxygen was increased already in the children of ARM patients. An increasing optical density of xanthophyll was determined after lutein supplementation. Differences in fluorescence lifetime were determined between ARM patients and healthy subjects, but their interpretation requires investigations of cell or of organ model cultures. CONCLUSIONS: The described methods permit in vivo basic investigations of ARM and can be considered as impulses for the development of diagnostic devices.

A wide-field, high-resolution ophthalmoscopic contact lens.

A new inverted-image ophthalmoscopic contact lens provides 2X laser spot magnification and a 117 degrees degree instantaneous field of view. It has three times the resolution of very wide-field, inverted-image ophthalmoscopic contact lenses to permit effective use of higher slit-lamp magnifications. The lens was designed for transpupillary thermotherapy with large lesions and panretinal photocoagulation with hazy ocular media.

Teleophthalmology link between a primary health care centre and a reference hospital.

We have evaluated a teleophthalmology service linking a primary health care centre and an eye clinic at a reference hospital. General practitioners at the primary care centre serving a population of 15,000 and ophthalmologists at the reference hospital participated in this study. Eye fundus digital images were taken from 278 eye fundi of 139 consecutive patients with clinical conditions that could potentially produce fundus alterations. Fundus images were obtained with a non-mydriatic fundus camera (Canon CR6-45M) and were electronically sent reference hospital where ophthalmologist inspected the images and returned the diagnosis. In 18 patients (13%) the images did not have good enough quality to exclude eye fundus lesions. In 24 patients (17%) clear eye fundus alterations were found in at least one eye. In 14 patients (10%) there were image features suggesting retinal alterations that could not be confirmed by image inspection. Media opacity (13 eyes, 5%, seven patients, 5%) was the most common cause of poor image quality. The most difficult assessment was the evaluation of optic nerve head cupping. Retinal oedema was not observable in the digital images. In our experience teleopthalmology services seem to be an effective alternative for eye fundus diagnosis and patient follow-up.

Ultrasonographic evaluation of optic disc swelling: comparison with CSLO in idiopathic intracranial hypertension.

PURPOSE: To determine the accuracy and reproducibility of ultrasonographic (US) readings of optic disc elevations in patients with papilledema compared with confocal scanning laser ophthalmoscope (CSLO) measurements. METHODS: One randomly selected eye of 22 patients with idiopathic intracranial hypertension (IIH) and a variable degree of optic disc swelling underwent five and three repeated measurements of disc height using high-resolution ultrasonography (Biovision unit; Quantel Medical, Clermont-Ferrand, France) and CSLO (Heidelberg Retina Tomograph [HRT]; Heidelberg Engineering, Heidelberg, Germany), respectively. The same procedure was assessed in 14 subjects with variable degrees of physiologic optic disc cupping. US and HRT measurements from each group were individually compared with each other to estimate the accuracy of US readings in both disc conditions in comparison with HRT data. RESULTS: Ultrasonographic readings were positively correlated with HRT measurements in both swollen (r = 0.62, P: = 0.002) and excavated disc (r = 0.84, P: < 0.0002). The 95% limits of agreement between the instruments were 0.24 +/- 0.59 mm (mean +/- 2 SD) and 0. 05 +/- 0.3 mm for swelling and cupping measurements, respectively. The coefficient of variation was 7.63% and 1.8% for swelling and 7. 93% and 5.91% for cupping, with US and HRT, respectively. CONCLUSIONS: The results indicate that US and CSLO readings are correlated i: both disc swelling and cupping conditions, but to a different extent because of a significant discrepancy in papilledema. US assessment can be considered highly reproducible. Combined US and HRT optic disc analysis may be recommended in papilledema evaluation as long as a better correlation can be demonstrated in further studies.

The sensitivity and specificity of direct ophthalmoscopic optic disc assessment in screening for glaucoma: a multivariate analysis.

BACKGROUND: Previous studies have shown that the cup:disc (C/D) ratio has limited sensitivity and specificity. Improved sensitivity and specificity has been found with combinations of disc parameters using stereophotography or disc imaging, but the extent to which these studies reflect what can be achieved by direct assessment is unclear. The purpose of this paper is to report the sensitivities and specificities of a range of disc parameters, both in isolation and in combination, as graded during clinical examination with direct ophthalmoscopy. METHODS: Sixty-seven patients with newly diagnosed primary open angle glaucoma and 145 non-glaucomatous subjects were examined by direct ophthalmoscopy. The following features of the optic disc were graded: vertical and horizontal C/D ratios (uncorrected for disc size), narrowest rim width, presence/absence of disc haemorrhage, focal pallor of the neuroretinal rim, parapapillary atrophy, steepness of the cup-edge and presence/absence of baring of the lamina cribrosa. Subjects were validated as glaucomatous/non-glaucomatous on the basis of visual fields, independently of the results of optic disc gradings. Multiple logistic regression modelling was used to evaluate the effectiveness of combinations of disc parameters. RESULTS: Sensitivities and specificities are limited for all features when considered in isolation. The 'cupping' parameters have the highest sensitivities and specificities but no single cut-off criterion for these parameters has both high sensitivity and specificity. Multiple logistic regression modelling indicated that two disc parameters in combination, narrowest rim width and parapapillary atrophy, were independently associated with glaucoma and achieved best prediction. Combining information from these parameters achieved a sensitivity of 81% (95% CI = 69-89%) and a specificity of 90% (95% CI = 84-95%), a level of discrimination that is not significantly better than narrowest rim width alone in terms of area under the receiver operator characteristic (ROC) curve. CONCLUSION: Disc assessment during clinical examination with direct ophthalmoscopy can achieve comparable sensitivities and specificities with those previously reported for stereophotographic assessment or visual fields screening. However, since the diagnostic accuracy of disc assessment in isolation is inadequate for screening, a combined test strategy is necessary.