Exacerbation of central serous chorioretinopathy during trauma-confronting psychotherapy- a case report.

BACKGROUND: Psychotherapy for post-traumatic stress disorder, in particular trauma-confronting psychotherapy, can be associated with increased stress. However, research on the somatic impact and psychosomatic interactions of these psychological stress reactions is lacking. We report on a 43-year old man whose central serous chorioretinopathy exacerbated upon trauma-confronting psychotherapy. CASE PRESENTATION: We report on a man with pre-diagnosed, asymptomatic central serous chorioretinopathy who underwent inpatient psychosomatic therapy. He disclosed a history of sexual abuse by a family member and consequently showed intrusions, flashbacks, nightmares, avoidance behavior, and hyperarousal. Thus, we diagnosed post-traumatic stress disorder. After a stabilization phase, he underwent trauma-focused psychotherapy including trauma confrontation. In the course of this treatment, acute vision loss with blurred vision and image distortion of his right eye occurred. An ophthalmologic visit confirmed a relapse of a pre-diagnosed central serous chorioretinopathy. The analysis of stress biomarkers showed a decrease in testosterone levels and a noon peak in diurnal cortisol secretion, which is indicative of a stress reaction. CONCLUSION: Central serous chorioretinopathy may exacerbate upon psychotherapeutic treatment. In this case, an exacerbation of chorioretinopathy was observed in direct relation to the therapeutic intervention. Psychotherapists and ophthalmologists should collaborate in the psychotherapeutic treatment of patients with chorioretinopathy. Our case demonstrates the need to consider the possible increased stress levels during psychotherapy and resulting physical side effects, such as exacerbation of an existing condition. It is advisable to adjust the level of generated stress particularly well in the presence of stress-inducible physical diseases. Our case is a good example of the interplay between psychological and physical stress.

Pattern electroretinogram, blue-yellow visual evoked potentials and the risk of developing visual field defects in glaucoma suspects: a longitudinal "survival" analysis with a very long follow-up.

PURPOSE: Estimating glaucoma suspects' risk for visual field defects helps to avoid under- and over-treatment. In this retrospective, longitudinal cohort study with a very long follow-up, we studied whether pattern electroretinograms (PERG) amplitudes and blue-on-yellow visual evoked potential (BY-VEP) latencies can predict visual field defects. METHODS: Participants of the Erlangen Glaucoma Study were examined with PERG and BY-VEP between 9/1991 and 8/2001. Stimuli were created using an optical bench with Maxwellian view and consisted of vertical gratings (0,88 cpd) in a 32° field for both PERG and BY-VEP. Patients were treated according to clinical standards and performed standard automated perimetry (SAP) annually. Retrospectively, patients with normal SAP at baseline were selected. Primary endpoint was conversion to perimetric glaucoma. Predictive value was modeled using Kaplan-Meier analyses and a multivariate cox proportional hazards model with the continuous variables PERG amplitude, BY-VEP peak time and SAP square-root of loss variance (sLV) after stratification for Jonas classification of the optic discs. RESULTS: Of 412 patients (288: Jonas 0, 103: I, and 21: II; baseline age: 20-60 years), 65 converted to perimetric glaucoma during follow-up (0.5-23.3 years; median 5.5 years). Optic disc classification was a strong risk factor for conversion (log rank p < 0.0001), and patients with more advanced changes progressed earlier. In the multivariate analysis (log rank p = 0.005), only PERG amplitude remained an independent risk factor after stratification for optic disc morphology (p = 0.021), with a ~ 30% higher risk per µV amplitude decrease. CONCLUSIONS: PERG helps to estimate glaucoma suspects' risk for visual field defects.

Bilateral Acute Macular Neuroretinopathy (AMN) after COVID-19 and its Clinical Course. / Bilaterale akute makuläre Neuroretinopathie (AMN) nach COVID-19 und Verlauf.

Acute macular neuroretinopathy (AMN) is a rare disease entity. It is mainly observed in young women with a history of influenza-like infection or who have been taking oral contraceptives for several years. Patients typically describe subjective visual deterioration and mono- or bilateral paracentral relative scotomas. In some cases, funduscopic ophthalmic examination may reveal subtle sharply demarcated flat lesions of reddish-brown or orange colour in the macular region. Diagnosis is usually made by near-infrared fundus imaging which shows hyporeflective areas, and SD-OCT imaging which manifests changes in the outer retinal layers. In the following, three patient cases with bilateral AMN are described which occurred in direct temporal relationship to a recent SARS-CoV-2 infection.

Maternal SARS-CoV-2 infection during pregnancy: possible impact on the infant.

The risk and potential consequences of mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy are still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Two PCR-confirmed perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded. In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, drug use, or maternal disease during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants.Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as support COVID-19 vaccination recommendations for pregnant women. Trial registration number: NCT04741412. Date of registration: November 18, 2020 What is Known: •Materno-fetal transmission of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) during pregnancy has rarely been reported so far, but was demonstrated in isolated cases. What is New: •In a study of complete households with documented SARS-CoV-2 infection, including a cohort of pregnant women, we observed perinatal coronavirus transmission at a higher frequency than expected. •We also describe a newborn boy with an eye malformation reminiscent of rubella embryopathy but associated with early gestation SARS-CoV-2 infection of his mother. •A coronavirus-related embryopathy, reported here for the first time, is a finding that requires further investigation.

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation.

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT-angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic ß2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.

Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue.

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell's score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell's score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.

Are There Static-Structural Biomarkers for Glaucoma with OCT? / Gibt es statisch-strukturelle Biomarker bei den Glaukomen mit der OCT?

Glaucomas lead to uniform, specific and slowly developing atrophy of the optic nerve with progressing visual field defects in late stages. Early diagnosis is challenging, but necessary as optic nerve damage is irreparable. Biomarkers with structural optical coherence tomography (OCT) flag optic atrophy but do not prove to be specific in the differential diagnosis to other forms of optic atrophy. Combination of OCT parameters and their correlation to other variables facilitate glaucoma diagnosis. Use of artificial intelligence (AI) in structural OCT images may prove to be superior and as biomarker more specific to thickness measurements of neuronal tissues alone.

Applications of Artificial Intelligence in Optical Coherence Tomography Angiography Imaging.

Optical coherence tomography angiography (OCTA) and artificial intelligence (AI) are two emerging fields that complement each other. OCTA enables the noninvasive, in vivo, 3D visualization of retinal blood flow with a micrometer resolution, which has been impossible with other imaging modalities. As it does not need dye-based injections, it is also a safer procedure for patients. AI has excited great interest in many fields of daily life, by enabling automatic processing of huge amounts of data with a performance that greatly surpasses previous algorithms. It has been used in many breakthrough studies in recent years, such as the finding that AlphaGo can beat humans in the strategic board game of Go. This paper will give a short introduction into both fields and will then explore the manifold applications of AI in OCTA imaging that have been presented in the recent years. These range from signal generation over signal enhancement to interpretation tasks like segmentation and classification. In all these areas, AI-based algorithms have achieved state-of-the-art performance that has the potential to improve standard care in ophthalmology when integrated into the daily clinical routine.

OCT Angiography as an Interdisciplinary Diagnostic Tool for Systemic Diseases. / OCT-Angiografie als interdisziplinäres Diagnostikum für Systemerkrankungen.

In recent years, OCT angiography (OCT-A) has emerged as a well established imaging modality of the retina. This allows non-invasive visualisation of the retinal circulation at a micrometre scale in eye disorders and systemic diseases with potential ocular involvement. This review summarises the current state of this topic.

[Clinical Decision Making for Treatment of Diabetic Macular Oedema with DEX Implant: a Consensus Paper]. / Klinische Entscheidungsfindung bei der Behandlung des diabetischen Makulaödems mit DEX-Implantat: ein Konsenspapier.

BACKGROUND: Currently two intravitreally applied corticosteroids (dexamethasone and fluocinolone) are licensed in Germany for treatment of diabetic macular oedema (DME). The use of DEX implant for DME in daily clinical practice has not been defined in detail. Following a Delphi panel survey, a group of retina experts set out to come up with a consensus for use of the DEX implant in DME. MATERIAL AND METHODS: International and national treatment recommendations were identified from the literature. A steering group generated a catalogue of 72 statements on the aetiology and pathogenesis of DME, therapy with DEX implant, use of DEX implant in patients previously treated with VEGF-inhibitors, use of DEX implant in combination therapy, safety of DME therapies as well as patients' burden of treatment. Twenty-two ophthalmologists from private practice and 6 hospital ophthalmologists participated in the Delphi panel via Survey Monkey. Consensus was reached if at least 75% of participants agreed or disagreed with a statement. Statements for which consensus was not reached were discussed once more during the expert consensus meeting and a vote was taken. Based on these results a treatment algorithm for foveal DME was proposed. RESULTS: If a patient does not show sufficient response after 3 - 6 months of anti-VEGF treatment (visual acuity gain of < 5 ETDRS letters or reduction of central retinal thickness ≤ 20%), a switch to DEX implant should take place. DEX implant is also suitable in eyes with longer presentation of DME, showing e.g. massive lipid exudates. DEX implant is suitable as first-line therapy especially in pseudophakic patients, patients unwilling or able to comply with tight anti-VEGF injection intervals or patients with known vascular diseases. With fixed control visits every 4 - 8 weeks, use of DEX implant is flexible and individual. Decision parameters for repeated use should be visual acuity, retinal thickness and intraocular pressure. Treatment of both eyes on the same day should not take place. CONCLUSION: The algorithm presented reflects survey as well as expert discussion results and may differ from recommendations issued by the German professional society. The consensus recommendations for the treatment of DME generated during the survey and meeting of retina experts are intended to guide use of DEX implant in daily practice.

Differential Effects of Aging in the Macular Retinal Layers, Neuroretinal Rim, and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: We determined the differential aging effects of the inner 6 layers of the macula in contrast to the minimum neuroretinal rim width (MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness. DESIGN: Cross-sectional, multicenter study. PARTICIPANTS: An approximately equal number of white subjects with a normal ocular and visual field examination in each decade group from 20 to 90 years. METHODS: OCT of the macula, optic nerve head, and peripapillary retina. MAIN OUTCOME MEASURES: Sectoral measurements of the inner 6 layers of the macula; age-related decline of each of these layers; strength of the associations with age of the macular parameters, MRW, and peripapillary RNFL thickness; and association between ganglion cell layer (GCL) thickness and MRW and peripapillary RNFL thickness. RESULTS: The study sample comprised 1 eye of 246 subjects with a median (range) age of 52.9 (19.8-87.3) years. Of the 6 layers, there was a statistically significant decline with age of only the GCL, inner plexiform layer, and inner nuclear layer thickness with rates of -0.11 µm/year, -0.07 µm/year, and -0.03 µm/year, respectively. These rates corresponded to 2.82%, 2.10%, and 0.78% loss per decade, respectively, and were generally uniform across sectors. The rate of loss of MRW and peripapillary RNFL thickness was -1.22 µm/year and -0.20 µm/year, corresponding to 3.75% and 2.03% loss per decade. However, the association of GCL thickness change with age (R2 = 0.28) was approximately twice that of MRW and RNFL thickness (R2 = 0.14 for each). CONCLUSIONS: In concordance with histopathologic studies showing age-related loss of retinal ganglion cell axons, we showed a significant decline in GCL thickness, as well as MRW and peripapillary RNFL thickness. The stronger relationship between aging and GCL thickness compared with the rim or peripapillary RNFL may indicate that GCL thickness could be better suited to measure progression of structural glaucomatous loss.

OCT Angiography: Measurement of Retinal Macular Microvasculature with Spectralis II OCT Angiography - Reliability and Reproducibility.

AIM: The aim of the present study was to investigate the reliability of macular microvasculature measurements in normal subjects by Heidelberg Spectralis II optical coherence tomography angiography (OCT-A) in combination with a newly made software. SUBJECTS AND METHODS: This prospective study included 23 eyes of 23 persons from the Erlangen Glaucoma Registry (ISSN 2191-5008, CS-2011; NTC00494923). The subjects underwent a complete clinical, standardized ophthalmologic examination to rule out any eye disease. En face OCT-A imaging was done using Heidelberg Spectralis II OCT (Heidelberg, Germany). Images were recorded with a 15 × 15° angle and a lateral resolution of 5.7 µm/pixel, resulting in a retinal section of 2.9 × 2.9 mm. The Erlangen-Angio-Tool (EA-Tool) OCT-A application performed multiple segmentations, allowing analysis of the vessel density in 12 segments. The software was coded in MATLAB. Macular data on the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were exported into the application and analyzed separately. The EA-Tool calculated the percentage of "white area" in the "total area" of the region of interest, called vessel density. Foveolar avascular zones (FAZs) of the SVP, ICP, and DCP were calculated manually. To investigate the reproducibility of the new software, individual scans (SVP, ICP, and DCP) were analyzed twice with the EA-Tool and intraclass coefficients (ICCs) of the vessel density values were calculated. Statistical analysis was performed with SPSS version 21.0. RESULTS: The mean vessel density of the SVP ranged between 30.4 and 33.5, that of the ICP between 20.9 and 24.7, and that of the DCP between 23.5 and 27.6. Bland-Altman plots showed a good reliability of two consecutive scans of each sector (S1-S12) in the SVP, ICP, and DCP. Testing reproducibility, no statistically significantly different sectorial coefficients of variation of the SVP, ICP, and DCP were observed (p > 0.05). The mean FAZ area of the SVP was 0.43 ± 0.16 mm2, that of the ICP 0.28 ± 0.1 mm2, and that of the DCP 0.44 ± 0.12 mm2. CONCLUSIONS: Spectralis OCT II, in combination with the semiautomated vessel density software EA-Tool, showed good or even excellent ICCs in 75% of all segments of the SVP, ICP, and DCP. The ICCs for the FAZ area in the SVP, ICP, and DCP were excellent.

[Optical Coherence Tomography in Glaucomas: Tips and Tricks]. / OCT-Diagnostik beim Glaukom: Tipps & Tricks.

High-resolution optical coherence tomography (OCT) with spectral-domain or swept-source techniques has become a mainstay in glaucoma and progression diagnosis. Imaging and morphometry of ganglion cell (GCL) and retinal nerve fiber (RNF) layer thickness and Bruch's membrane based minimum neuroretinal rim width (BMO-MRW) measurement allow the detection of pathologic changes. Graphic display of these measurements facilitate a comparison with normative data. False positive (red disease) and false negative (green disease) results represent pitfalls in OCT diagnosis. Pathologies of the posterior pole either caused by glaucoma or non-glaucoma associated changes of optic disc and retina play an important role. Epiretinal gliosis, age related macular degeneration and cystoid retinal changes cause measuring artefacts. A careful inspection of OCT B-scans is mandatory to detect these changes. Highly myopic eyes, underrepresented in normative databases cause changes resembling glaucoma and challenge the OCT glaucoma diagnosis. Neurological diseases present an important differential diagnosis when atrophy of neuroretinal tissue and ganglion cells occur. The location of the atrophy and the relationship of GCL, RNF and BMO-MRW changes may help in differential diagnosis. Sensory tests and imaging of the brain are mandatory in these cases. Drusen and disc edema cause thickening of BMO-MRW and may be followed by loss of RNF and GCL. Again a close observation of OCT B-scans and fundus may help to find the correct diagnosis. Good image quality, knowledge of OCT pathologies and technique of OCT imaging may help to avoid pitfalls in OCT glaucoma diagnosis.

Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis.

PURPOSE: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease. METHODS: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study. RESULTS: Using exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice. CONCLUSION: This study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.

[Retinal nerve fiber layer thickness measurements with optical coherence tomography in glaucoma patients and healthy controls]. / Schichtdickenmessungen der retinalen Nervenfaserschicht mit optischer Kohärenztomografie bei Glaukompatienten und Gesunden.

Thickness measurements of the retinal nerve fiber layer in glaucomas have become an important tool for diagnosis and follow-up of progression. High image resolution and advanced evaluation algorithms led to this achievement. In the following OCT anatomy, imaging technique, normative values, monitoring of progression and the influence of artefacts on OCT measurements are matter of discussion. Knowledge of capabilities and pitfalls of RNF imaging with OCT should help to integrate this technique into daily patient routine.

[26 Years of the Erlangen Glaucoma Registry: Demographic and Perimetric Characteristics of Patients Through the Ages]. / 26 Jahre Erlanger Glaukomregister: demografische und perimetrische Charakteristika der Patienten im Wandel der Zeit.

BACKGROUND: The history of the Erlangen Glaucoma Registry goes back 26 years. In this study, we present retrospective demographic and perimetric data on the initial visit of patients with ocular hypertension (OHT), pre-perimetric (prePOAG) and perimetric primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) and secondary open-angle glaucoma (SOAG) and correlate these results with the latest perimetric data. MATERIAL AND METHODS: 1406 (754 patients) of the Erlangen Glaucoma Registry (EGR; NTC00494923) were investigated retrospectively between 1991 and 2016 covering: demographic data (age, visual acuity, intraocular pressure [IOP]), diagnosis and perimetric characteristics (mean defect [MD], loss variance [LV]) at the initial visit and the latest perimetric data. RESULTS: (1) 558 eyes of OHT, 347 prePOWG, 236 POAG, 161 NTG and 104 SOWG were recruited in the Erlangen Glaucoma Registry between 1991 and 2007. (2) The initial age was significantly lower for OHT (43.79 ± 13.64) than for perimetric open-angle glaucoma (NTG: 54.46 ± 11.41, p < 0.001; POAG: 54.00 ± 11.27, p < 0.001; SOAG: 47.92 ± 12.37, p = 0.008). Patients with prePOAG (48.62 ± 11.98) were significantly younger than patients with POAG/SOAG (p < 0.001). (3) The best corrected visual acuity was better for OHT (1.04 ± 0.14, p < 0.001) and prePOAG (1.05 ± 0.15, p < 0.001) than for POAG (0.95 ± 0.16), SOAG (0.93 ± 0.23) and NTG (0.93 ± 0.18). (4) Initial IOP was significantly higher for OHT (19.08 ± 2.25 mmHg), prePOAG (19.18 ± 3.90 mmHg), POAG (18.29 ± 4.11 mmHg) and SOAG (18.57 ± 5.34 mmHg) than for NTG (15.23 ± 2.83 mmHg, p < 0.001). (5) Since 1991, increasing numbers of patients with POAG and SOAG were seen at the initial visit. (6) Trend for MD and LV between 1991 and 2016: a trend for increasing MD at the initial visit was detected for prePOAG and POAG, yet OHT, NTG and SOAG showed a decreasing trend for MD at the initial visit. All patient groups showed perimetric progression. CONCLUSION: Since its start in 1991, the patients of the Erlangen Glaucoma Registry exhibited perimetric progression up to the year 2016, although antiglaucomatous therapy was re-evaluated and optimised if target IOP was not achieved.

Structural changes of macular inner retinal layers in early normal-tension and high-tension glaucoma by spectral-domain optical coherence tomography.

PURPOSE: Assessment of the diagnostic ability of segmented macular inner retinal layer thickness and peripapillary retinal nerve fiber layer (pRNFL) measured by spectral-domain optical coherence tomography (SD-OCT) in patients with normal-tension (NT) and high-tension (HT) perimetric and preperimetric glaucoma. METHODS: The 212 participants included 45 healthy subjects, 55 patients with ocular hypertension, 56 patients with preperimetric glaucoma, and 56 patients with perimetric glaucoma. The preperimetric and perimetric groups were further subdivided into NT and HT groups. Sectoral and global thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (mGCL), inner plexiform layer (mIPL), ganglion cell complex (mGCC), and pRNFL were measured using SD-OCT (Spectralis, Heidelberg Engineering, Germany). Diagnostic performance was ascertained by sectoral and global comparison of the sensitivities at specificity ≥ 95%. RESULTS: For all layers, the largest thickness decrease was reported in the HT perimetric group. In all groups, the sensitivities of mGCL showed a comparable diagnostic value to pRNFL in order to distinguish between healthy subjects and glaucoma patients. In the perimetric group, mGCL (85.7%) exhibited higher sensitivities than mRNFL (78.6%) and mGCC (78.6%). Both mRNFL and pRNFL demonstrated equal diagnostic performance in the HT perimetric group (88.5 and 96.2%), in the NT groups, mRNFL was inferior to all other layers. CONCLUSION: The sensitivities of mGCL and mRNFL were comparable to the sensitivities of pRNFL. In clinical application, mGCL and mRNFL, with a focus on the temporal and inferior sectors, may provide a convincing supplementation to pRNFL. CLINICAL TRIAL REGISTRATION: Erlangen Glaucoma Registry www.clinicaltrials.gov ID: NCT00494923.

Comparison of frequency doubling and flicker defined form perimetry in early glaucoma.

PURPOSE: To compare perimetric data based on the second-generation frequency doubling technology (FDT) and on flicker defined form (FDF) stimulation in early glaucoma patients. METHODS: Seventy-two experienced glaucoma patients and 50 healthy subjects of the Erlangen Glaucoma Registry participated in the study. The definition of glaucoma was solely based on optic disc appearance. All patients underwent FDF perimetry (HEP), FDT perimetry (Matrix), standard automated perimetry (SAP, Octopus), and peripapillar measurements of the RNFL thickness (Spectralis OCT). Exclusion criteria were: mean defect (MD) in SAP > 6 dB, eye diseases other than glaucoma, or non-reliable FDF or FDT measurements. Statistical analyses included comparison of the standard indices and correlations between methods. Venn-diagrams show the number of patients with abnormal results in HEP, Matrix, SAP, and mean RNFL thickness. RESULTS: Mean defect data from FDT and FDF perimetry were strongly correlated (R = -0.85, P <0.001). In this cohort of early glaucoma patients, the MD values were 6.1 ± 5.0 dB (FDF) and 4.5 ± 4.1 dB (FDT). Sensitivity in this patient group was 65 % for FDF-MD, 60 % for FDT-MD, and 60 % for RNFL-thickness, all at a specificity of 95 %. The correlation analysis between local RNFL thickness and corresponding visual defects revealed significant Spearman correlation coefficients for the arcuate bundles of the visual field (FDF-inferior: R = -0.65, FDF-superior: R = -0.74, FDT-inferior: R = -0.55, FDT-superior: R = -0.72). CONCLUSION: FDF and FDT stimulations can be used to detect patients with early glaucoma. Combined consideration of RNFL thickness and results from one of these perimetric tests can increase the total number of detected patients.