Do biometric parameters improve the quality of optic nerve head measurements with spectral domain optical coherence tomography?

BACKGROUND: Spectral domain optical coherence tomography (SD-OCT) is a widely applied non-invasive technique for evaluating optic nerve head parameters. The aim of this study was to evaluate the impact of biometric parameters such as the spherical equivalent (SE) and the anterior corneal curvature (ACC) on the peripapillary retinal nerve fiber layer (pRNFL), Bruch's membrane opening (BMO), and the minimum rim width (MRW) measurements performed by spectral domain optical coherence tomography (SD-OCT) in glaucomatous and healthy eyes. METHODS: In this cross-sectional, case-control prospective pilot study, the glaucoma group consisted of 50 patients with previously diagnosed and treated glaucoma and one healthy group of 50 subjects. Two consecutive examinations of pRNFL, BMO, and MRW with SD-OCT for every patient were performed without ACC and objective refraction (imaging 1) and with them (imaging 2). RESULTS: The interclass correlation coefficient (ICC) reflected high agreement between imaging 1 and imaging 2 in both groups. The ICC in the glaucoma and healthy groups for pRNFL (0.99 vs. 0.98), BMO (0.95 vs. 0.97), and MRW (1.0 vs. 1.0) was comparable. CONCLUSIONS: Our preliminary data from a small number of eyes showed that the measurements of pRNFL, MRW, and BMO reflected high agreement between both imaging techniques with ACC and objective refraction and without these parameters in subjects with a refractive error up to ± 6.0 diopters. Further studies with participants with higher refractive error are necessary to evaluate the impact of biometric parameters such as SE and ACC on measurements with SD-OCT.

Peripapillary Choroidal Thickness and Choroidal Area in Glaucoma, Ocular Hypertension and Healthy Subjects by SD-OCT.

BACKGROUND: The exact pathogenesis of open angle glaucoma and ocular hypertension remains unclear. Hemodynamic influences are discussed as potential risk factors and the choroid may play an important role in the pathogenesis of open angle glaucoma or ocular hypertension. The current study investigates peripapillary choroidal thickness and choroidal area in patients with open angle glaucoma, subjects with ocular hypertension and healthy subjects using spectral-domain OCT. It furthermore assesses the association between peripapillary choroidal thickness and age, central corneal thickness, refractive error and intraocular pressure. PATIENTS AND METHODS: Prospectively recorded data of 213 eyes of 177 open angle glaucoma patients, 73 eyes of 50 subjects with ocular hypertension and 152 eyes of 116 healthy control subjects were analyzed by fitting a linear mixed model including age and disease. RESULTS: Peripapillary choroidal thickness was thinnest in glaucoma patients (125 µm), followed by healthy subjects (127 µm) and ocular hypertensive subjects (135 µm). A marginally significant difference was present between ocular hypertension and glaucoma (p=0.059). Thickest choroids were found superiorly and thinnest choroids inferiorly. Choroidal area was highest in the supero-nasal and lowest in the infero-temporal sectors. Choroidal thickness decreased with age, no significant correlation was evident between peripapillary choroidal thickness and refractive error or intraocular pressure. Peripapillary choroidal thickness and central corneal thickness are significantly negative correlated in healthy subjects. CONCLUSIONS: There is a trend towards thicker choroids in ocular hypertensive subjects compared to healthy subjects or glaucoma patients. Thickest choroids are found superiorly, thinnest inferiorly. Interestingly, choroidal area is thinnest in the temporal-inferior sector, one of the regions where glaucomatous damage tends to start.

[ChatGPT and the German board examination for ophthalmology: an evaluation]. / ChatGPT und die deutsche Facharztprüfung für Augenheilkunde: eine Evaluierung.

PURPOSE: In recent years artificial intelligence (AI), as a new segment of computer science, has also become increasingly more important in medicine. The aim of this project was to investigate whether the current version of ChatGPT (ChatGPT 4.0) is able to answer open questions that could be asked in the context of a German board examination in ophthalmology. METHODS: After excluding image-based questions, 10 questions from 15 different chapters/topics were selected from the textbook 1000 questions in ophthalmology (1000 Fragen Augenheilkunde 2nd edition, 2014). ChatGPT was instructed by means of a so-called prompt to assume the role of a board certified ophthalmologist and to concentrate on the essentials when answering. A human expert with considerable expertise in the respective topic, evaluated the answers regarding their correctness, relevance and internal coherence. Additionally, the overall performance was rated by school grades and assessed whether the answers would have been sufficient to pass the ophthalmology board examination. RESULTS: The ChatGPT would have passed the board examination in 12 out of 15 topics. The overall performance, however, was limited with only 53.3% completely correct answers. While the correctness of the results in the different topics was highly variable (uveitis and lens/cataract 100%; optics and refraction 20%), the answers always had a high thematic fit (70%) and internal coherence (71%). CONCLUSION: The fact that ChatGPT 4.0 would have passed the specialist examination in 12 out of 15 topics is remarkable considering the fact that this AI was not specifically trained for medical questions; however, there is a considerable performance variability between the topics, with some serious shortcomings that currently rule out its safe use in clinical practice.

[Optical coherence tomography (OCT) in glaucoma diagnostics]. / Stellenwert der optischen Kohärenztomografie (OCT) für die Glaukomdiagnostik.

Optical coherence tomography (OCT) provides high resolution objective and quantitative measurements of the optic disc parameters and RNFL thickness and has been widely used for detection of glaucomatous damage and disease progression. The recent introduction of spectral domain (SD)-OCT technology, also known as Fourier domain (FD)-OCT offers significant advantages over the previous time domain (TD)-OCT, allowing 3 D imaging of the retina and optic disc with ultra-high acquisition speed and ultra-high resolution. The higher resolution of (SD)-OCT offers enhanced visualisation and improved segmentation of the retinal layers, providing a higher accuracy in identification of subtle changes of the optic disc and RNFL thinning associated with glaucoma.

[Combined XEN and Baerveldt implant-principles and management of complications]. / Kombiniertes XEN-Baerveldt-Implantat ­ Prinzip und Management von Komplikationen.

The treatment of congenital glaucoma requires special expertise and often novel surgical approaches. The combined use of a XEN and a Baerveldt implant is an alternative to conventional tube implants and may be less harmful for long-term corneal endothelial damage. If this technique does not provide sufficient long-term control of intraorbital pressure (IOP), a direct implantation of the Baerveldt tube can be easily performed in a second intervention.

[Trabeculectomy with mitomycin C : Video article]. / Trabekulektomie mit Mitomycin C : Videobeitrag.

Trabeculectomy is the most proven method for the treatment of open angle glaucoma. The long-term results of this method show an 80% success rate in lowering intraocular pressure over 20 years. The surgical technique is demonstrated in detail with the help of a video of the operation and which is available online. For more than 15 years trabeculectomy has been performed with the use of antifibrotic substances, such as mitomycin C. Long-term treatment with antiglaucoma eyedrops leads to a proven inflammation of the conjunctiva and the ocular surface with an increase in lymphocytes, mast cells, and fibroblasts. Discontinuation of antiglaucoma therapy in turn allows regeneration of the ocular surface. From the knowledge gained from these histopathological studies it has been recommended to stop glaucoma treatment prior to glaucoma surgery and to pretreat the conjunctiva with eyedrops containing cortisone. Administration of nonsteroidal antiphlogistic substances or local steroids to the conjunctiva 4 weeks prior to surgery increases long-term success of the filtering bleb function.

Revision of encapsulated blebs after trabeculectomy: Long-term comparison of standard bleb needling and modified needling procedure combined with transconjunctival scleral flap sutures.

PURPOSE: To compare two surgical approaches for treating encapsulated blebs after trabeculectomy with mitomycin C, in terms of the development of intraocular pressure and progression of glaucoma in a long-term follow up: 1. bleb needling alone vs. 2. a combined approach of needling with additional transconjunctival scleral flap sutures, to prevent early ocular hypotony. METHODS: Forty-six patients with failing blebs after trabeculectomy with mitomycin C were enrolled in this study. Patients received either needling revision alone (group 1; n = 23) or a combined needling with additional transconjuctival flap sutures, if intraoperatively the intraocular pressure was estimated to be low (group 2; n = 23). Intraocular pressure (IOP), visual acuity, visual fields, and optic nerve head configuration by means of Heidelberg Retina Tomograph (HRT®) were analysed over time. Results from both groups were compared using Mann-Whitney U-test for single timepoints. RESULTS: IOP did not differ significantly between the two groups during follow-up at three months (P = 0.13), six months (P = 0.12), one year (P = 0.92) and two years (P = 0.57) after surgery. Furthermore, there was no significant difference in the course of glaucoma concerning the optic nerve anatomy between the two groups (Rim Area Change in the Moorfields Regression Analysis of HRT®) till two years after surgery (P = 0.289). No functional impairment in visual acuity and visual fields was found in the groups of the study. CONCLUSIONS: Single needling procedure is a standard successful method for restoring the function of encapsulated blebs. Postoperative hypotony represents a possible hazard, which can be minimized by additional transconjunctival flap sutures. Long-term results suggest that this modification is equally effective in lowering the IOP and preventing the progression of glaucoma as the standard needling procedure. To our knowledge this is the first study to investigate the long-term effect of tranconjunctival sutures for the prevention of hypotony.

Glaucoma detection using the GDx nerve fiber analyzer and the retinal thickness analyzer (RTA).

PURPOSE: To compare the ability of the nerve fiber analyzer (GDx) and the retinal thickness analyzer (RTA) to discriminate between glaucomatous and healthy eyes. METHODS: Thirty-seven glaucoma patients (early to moderate severity) and 34 healthy controls were included. Glaucoma patients were defined as those with two repeatable abnormal visual fields by automated perimetry within 1 year. All subjects were examined with a GDx scanning laser polarimeter and RTA. Twelve GDx retinal nerve fiber layer parameters and 12 RTA optic disk topography parameters were obtained. GDx and RTA measurements were compared between both experimental groups using t-tests. Areas under the receiver operating characteristic curves (AUROC) for discriminating between healthy and glaucomatous eyes using GDx and RTA parameters were calculated and compared, and sensitivities at >or=80% and >or=95% specificity were reported. RESULTS: Statistically significant differences between glaucomatous and healthy eyes were found for most GDx and RTA parameters. For GDx, the parameter with the largest AUROC for discriminating between healthy and glaucomatous eyes was the number (AUROC = 0.91, sensitivity = 85% at specificity = 84%, sensitivity = 73% at specificity = 95%). For RTA, the parameter with the largest AUROC was mean cup depth (AUROC = 0.79, sensitivity = 61% at specificity = 82%, sensitivity = 33% at specificity = 95%). The AUROC for the GDx number was significantly larger than the AUROC for RTA mean cup depth (p<0.05). CONCLUSIONS: GDx showed better discrimination and better sensitivities at fixed specificities than RTA. The currently available RTA optic disk analysis software likely cannot replace GDx RNFL analysis software for successful glaucoma diagnosis.

[Goldmann applanation tonometry and dynamic contour tonometry. Comparison of intraocular pressure measurements in the course of product certification according to EN ISO 8612:2001]. / Goldmann-Applanationstonometrie und dynamische Konturtonometrie. Vergleich der intraokularen Druckmessung im Rahmen einer Typprüfung nach EN ISO 8612:2001.

BACKGROUND: The aim of the study was to compare intraocular pressure (IOP) measurements between Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) during product certification according to the international requirements for ophthalmic instruments (tonometers, ISO 8612:2001). METHODS: The study included 160 eyes of 80 subjects. IOP measurements were performed four times consecutively on each instrument in randomized order. The difference of mean IOP measurements between GAT and DCT was analyzed. Furthermore, Bland and Altman analysis was performed to assess agreement between the instruments. RESULTS: The mean difference between DCT and GAT IOP measurements was 0.30+/-2.18 mmHg. At low to normal IOP values of 7-16 mmHg and higher IOP values of > or =23 mmHg, the difference between DCT IOP measurements and GAT IOP measurements increased in the opposite direction (1.44+/-1.59 mmHg and -1.47+/-2.57 mmHg). The Bland and Altman analysis revealed a fixed bias of -0.4+/-2.0 mmHg. CONCLUSIONS: The test tonometer DCT exceeds the requirements for the international standard for tonometers ISO 8612:2001. The results are valid for a central corneal thickness of 540+/-40 microm.

[Differentiation of ocular hypertension]. / Abgrenzung der okulären Hypertension.

The term ocular hypertension has been used for more than 30 years. It is defined as an elevated intraocular pressure above the statistical norm without detectable optic nerve head or visual field damage. The number of patients with ocular hypertension in Germany is estimated to be approximately 3-5 million. Increased intraocular pressure is a risk factor for conversion to primary open-angle glaucoma. Most patients with ocular hypertension (and no risk factors) can be followed on a regular basis without any treatment. Each visit should include measurement of intraocular pressure, optic nerve head examination with a slit lamp, imaging and perimetric examinations. Currently known risk factors are high intraocular pressure, higher age, myopia, a thin cornea and darkly pigmented skin. If risk factors are present, antiglaucomatous therapy is indicated.

Scanning laser polarimetry and retinal thickness analysis before and after laser in situ keratomileusis.

PURPOSE: To evaluate changes in retinal nerve fiber layer (RNFL) thickness after laser in situ keratomileusis (LASIK) using a scanning laser polarimeter with fixed corneal compensation (GDx) and the retinal thickness analyzer (RTA). METHODS: Thirty-eight eyes of 19 healthy subjects (10 female and 9 male; mean age 37.0-/+8.8 years) underwent GDx and RTA measurements before and after LASIK. All subjects revealed mild to high myopia (mean spherical refraction: -4.0-/+2.75 D). Measurements using GDx were followed by RTA measurements after pupil dilation. All measurements were performed the day before LASIK and 1 week postoperatively. RESULTS: GDx revealed a decrease in nerve fiber layer thickness measurements after LASIK, but did not reach statistical significance (p>0.05). Using RTA, mean RNFL thickness (MRNFL) and RNFL cross sectional area decreased significantly after LASIK (p=0.03 and p=0.02, respectively). CONCLUSIONS: Scanning laser polarimetry revealed a slight decrease in RNFL thickness measurements after LASIK. MRNFL and RNFL cross section were significantly lower after LASIK using RTA. The changes might be artifacts in a small group of myopic subjects.

[Reproducibility of measurements of the peripapillary retinal nerve fibre layer thickness. Optical coherence tomography versus retinal thickness analyzer]. / Reproduzierbarkeit der Messung der peripapillären Nervenfaserschichtdicke. Optische Kohärenztomographie versus Retinal Thickness Analyzer.

PURPOSE: The aim of this study was to compare the intra- and inter-examiner reproducibility of measurements obtained by optical coherence tomography (OCT) and retinal thickness analyzer (RTA). PATIENTS AND METHODS: During a period of 2 months, 22 eyes of 16 patients and 6 healthy subjects were included. Two examiners (EMH, RK) successively performed three measurements of the peripapillary retinal nerve fibre layer (RNFL) thickness with RTA and OCT. The reproducibility of three individual measurements of one examiner (intra-examiner) as well as the reproducibility of the measurements between both examiners (inter-examiner) was evaluated using the Friedman test and sign test. RESULTS: The average thickness of the peripapillary RNFL was 154.4 microm for the first investigator (EMH) and 155.1 microm for the other investigator (RK) measured with RTA. The results obtained by OCT were 137.3 microm (EMH) and 138.9 microm (RK), respectively, generally indicating a threefold smaller range. Comparing the three measurements of one single examiner, no appreciable intra-observer dependency neither for RTA (EMH: p=0.19, RK: p=0.95) nor for OCT (EMH: p=0.51, RK: p=0.62) was observed. Inter-examiner analysis for RTA and OCT also revealed an acceptable reproducibility. CONCLUSIONS: Measurements of peripapillary RNFL thickness using RTA and OCT exhibited intra- and inter-observer agreement.

[Laser in situ keratomileusis (LASIK) and scanning laser ophthalmoscopy]. / Laser-in-situ-Keratomileusis (LASIK) und Scanning-Laser-Ophthalmoskopie Originalien.

BACKGROUND: To determine the influence of Laser in situ keratomileusis (LASIK) on the measurements of retinal thickness and optic nerve head topography using the Retinal Thickness Analyzer (RTA). METHODS: RTA measurements were performed before and after LASIK. Forty-eight eyes of 25 healthy subjects were included. Mean age was 40.0+/-10.6 years. Mean preoperative refractive error (spherical equivalent) was -3.3+/-3.6 dpt, and 0.2+/-0.9dpt postoperatively. Correlation between ablation depth and duration and change of retinal thickness postoperatively was performed. All patients received a pachymetry preoperatively. RESULTS: Postoperatively, mean retinal nerve fiber layer thickness (MRNFL) and cross sectional area (RNFL cross section area) significantly decreased after LASIK (MRNFL preop: 0.18 mm, postop: 0.11 mm, P =0.026, RNFL cross section preop: 1.17 mm(2), postop: 0.71 mm(2), P =0.015). Ablation depth revealed a significant correlation with changes in retinal thickness measurements postoperatively (Delta MRNFL: Ablation depth, P =0.001, r=-0.5). Duration of the ablation was not significantly correlated to the MRNFL measurements postoperatively (P =0.27, r=-0.08). No correlation was found between the central corneal thickness and the change in retinal thickness after LASIK (P =0.51). CONCLUSION: Due to changes in corneal architecture after LASIK, measurements using RTA reveal a decrease in MRNFL and RNFL cross section area. These changes are likely artifacts. Further studies with a longer follow-up are desirable.

[Value of Heidelberg retinal tomography in glaucoma diagnostics]. / Stellenwert der Heidelberg-Retina-Tomographie in der Glaukomdiagnostik.

BACKGROUND: The Heidelberg retinal tomography (HRT) is a technique that has been used for more than 20 years for glaucoma diagnostics and management. Many hundreds of scientific investigations have tested the reliability and accuracy of HRT for the early diagnosis of glaucoma and just as many studies can be found on the detection of progression in glaucoma. It is still one of the leading imaging systems for the detection and follow-up of glaucoma. Hardware and statistical methods implemented for progression detection have been regularly updated by the company and internationally known glaucoma specialists. METHODS: Besides the analysis of stereometric parameters and trend analyses, the primary method for assessing glaucomatous change using the HRT is the topographic change analysis (TCA), a technique that compares the variability within a baseline examination to that between baseline and follow-up examinations.Furthermore, the flicker comparison enables detection of small topographic changes over time. CONCLUSION: The use of HRT does not replace clinical examinations but facilitates the assessment and management of glaucoma depending on observer experience. This imaging method will still have a significant value in the future for glaucoma diagnostics, with a special emphasis on assessment of progression.

The use of sucrose as a cryoprotective agent for the labile sheep erythrocyte-complement component--intermediate complex, EAC142.

Sucrose (15% w/v) was found to be a useful agent for cryopreservation of sheep erythrocytes in the intermediate state EAC142. The ordinarilly very labile SAC142, associated with the cells, did not decay to any appreciable degree during periods of storage of 1, 72 or 132 days at -65 to -70 degrees C. Recovery of erythrocytes after freezing and thawing varied. Our best recovery was 76.6% and the poorest was 43.0%. The poorest recoveries were obtained during the latter part of the 132 day experiment after the freezer malfunctioned on day 35 causing a temperature rise to -50 degrees C which lasted for 3 days. The average spontaneous lysis of cells before freezing and thawing was 5.6%. The average spontaneous lysis for cells which had been stored in the frozen state was 6.9%.

Mechanism of serum resistance among Brucella abortus isolates.

It was shown in this study that complement-resistant Brucella abortus used were unable to activate complement in the absence of specific antibody. Complement-resistant isolates possessed O-antigen, but complement-sensitive organisms used are O-antigen deficient. Since B. abortus LPS does not activate the alternative pathway of complement, we concluded that activation of bovine complement must be due to some other mechanism. In this study, it was shown that bovine C1 binds to the outer membrane proteins of B. abortus. Isolated outer membrane proteins of both smooth (O-antigen positive) and rough (O-antigen negative) B. abortus used bind to C1q. However, only rough isolates were killed by complement. All of the O-antigen positive B. abortus isolates were complement-resistant. We propose that O-antigen shields outer membrane proteins and blocks C1q binding.

Production of Brucella abortus-specific protein A-reactive antibodies (IgG2) in infected and vaccinated cattle.

The IgG2 anti-Brucella antibody response of cattle to Brucella vaccination and infection was measured. Three groups of animals were studied; Group 1 contained 11 non-vaccinated cows, Group 2, 17 cows vaccinated with a low dose of Strain 19 vaccine and Group 3, 17 cows vaccinated with a high dose of Strain 19 vaccine. All animals were challenged at Week 33 with an infectious isolate of B. abortus (Strain 2308). Studies of the IgG2 antibodies response indicated an absolute correlation between anti-Brucella IgG2 levels and infection of the animal. All animals showing reciprocal titers of greater than or equal to 3000 (16 of 45 tested) were found to be positive for the challenge organism at slaughter. Animals with reciprocal IgG2 titers less than or equal to 1000 (29 of 45 tested) were found to be negative for the challenge organism at the time of slaughter. The predictive value of IgG2 antibody levels for infection held for animals in all three groups and consequently this suggests that monitoring of specific IgG2 anti-Brucella antibody levels may be of value in detection of Brucella-infected cattle.

Failure of Brucella abortus lipopolysaccharide (LPS) to activate the alternative pathway of complement.

Bovine erythrocytes (E) coated with either crude or purified preparations of Brucella abortus LPS were not lysed by human complement (C) in the presence of the chelating agent ethyleneglycol-bis-N, N'-tetraacetic acid (EGTA). On the other hand, bovine red cells coated with Salmonella typhimurium LPS were lysed by human C in EGTA. B. abortus LPS preparations did not cause fluid phase human C consumption in the presence of calcium and magnesium ions. However, as expected, S. typhimurium LPS consumed C from human serum in a dose-dependent fashion. The results of these experiments indicate that B. abortus LPS differs from the Enterobacterial LPSs in that it cannot activate the alternative pathway of C in human serum. Furthermore, the failure of B. abortus LPS to consume C in the fluid phase in the presence of calcium and magnesium ions suggests that the LPS cannot cause antibody-independent activation of the classical pathway.

The use of a passive hemolysis system to evaluate the complement activities of six mammalian species.

A passive hemolysis assay system was developed which permitted comparisons of the hemolytic activities of complement (C) from six species. This system employs a single antigen and an antiserum raised in one species. Thus, variations resulting from different target antigens and those inherent in using antibodies (of different affinities and isotypes) raised in a variety of species were minimized. Of the erythrocytes (E) examined, those from horses and guinea pigs were most susceptible to lysis, and either would be suitable, as a tentative choice, for measuring C activity of a previously unstudied species. Horse serum had the lowest C activity of any of the sera tested. It lysed certain cells only at high concentrations, and the hemolytic activity dropped off sharply with minimal dilution. The data presented in this paper could also be used for selecting target E for C studies using direct lysis with antibodies raised against the cells.

Evaluation of serologic and cellular immune responses of cattle to a nonlipopolysaccharide antigen from Brucella abortus.

Cows naturally infected with Brucella abortus developed antibody (Ab) responses to a nonlipopolysaccharide antigen (NLA) purified from B abortus strain 1119-3. Sera from strain 19-vaccinated cows did not have detectable amounts of Ab. Weak lymphoproliferative responses to NLA were observed in blood mononuclear cell suspensions obtained from infected cows. There was no evidence of NLA-specific lymphoproliferation in cell suspensions from healthy cows. Nonlipopolysaccharide antigen binding to bovine blood mononuclear cells was observed by antigen-consumption assays and direct binding of radiolabeled antigen. Cells from infected cows bound less NLA than did cells from healthy cows when assays were conducted with intact blood mononuclear cell preparations (monocytes plus lymphocytes). Monocytes obtained from any group did not bind NLA. Purified B lymphocytes from infected and healthy vaccinated cows bound about 3 times more NLA than did T lymphocytes, but there were no apparent differences between the 2 groups in extent of binding. Results of the study indicate that bovine lymphocytes have binding sites for a NLA purified from B abortus strain 1119-3.