Disc Photographs Research Articles

Cup-to-Disc Ratio in Patients With Idiopathic Intracranial Hypertension Is Smaller Than in Normal Subjects?

We read with interest the article by Geddie et al (1) that might better have been titled “Cup-to-Disc Ratio in Patients With IIH and Frisén Grade 0-2 Is Smaller Than in Normal Subjects.” The authors should be commended for tackling a difficult and complicated study. There are a variety of obstacles with a study like this, but a main one is the inclusion of cases with optic disc edema. The authors state that grade 0-2 is minimal or resolved optic disc edema. Frisén Grade 2 can be mild or moderate but is usually not minimal edema. To test the hypothesis that there is no difference in the vertical cup-to-disc ratio between idiopathic intracranial hypertension (IIH) patients and normal controls, we analyzed data from our prospective study of 50 IIH patients (2). It is well known that as optic disc edema progresses, the optic cup fills in (3). So, in our analysis, we included only Frisén grade 0 papilledema. Twenty-one of our IIH patients had grade 0 optic disc edema at their final visit. The average cup size was 0.191 ± 0.14 in the right eye and 0.187 ± 0.13 in the left eye. This compares to the results of Geddie et al of 0.143 in the right eye and 0.127 in the left eye. Another issue is that differences in cup size relate to the grading process itself. This is more subjective than it appears. The grader (B.E.G.) only graded papilledema eyes. No controls were intermixed. Was the grader aware of the hypothesis being tested? If so, could this have influenced the results? It would appear necessary in a study like this for masked graders to evaluate intermixed controls and these values be used rather than controls graded by others. Another confounding factor is that it has been our experience that some swollen optic discs never completely defervesce following treatment for IIH, even when they are technically grade 0. The mechanism may be either similar to skin not returning to normal after prolonged stretching or the effect of the presence of intermittent, prolonged, mild, increased intracranial pressure. This mechanism, we believe, can also result in a smaller optic cup appearance in IIH. In our opinion, the study of Geddie et al does not adequately demonstrate that cup-to-disc ratio is smaller in IIH patients. As stated above, this is a complicated and difficult study to undertake. Ideally, one would want to grade optic disc photographs taken before the onset of IIH. Given that this is not realistic, we urge the authors to reanalyze their data set as follows: Grade a large number of intermixed normal controls with proportions intermixed to reflect racial differences in cup size. Use 3 graders masked to the diagnosis and take the mean of the measures. Limit the analysis to grade 0 optic disc edema, where the disc does not appear elevated on stereoscopic fundus photographs. If this is performed and their results are the same, we would have more confidence in their title and conclusions. Michael Wall, MD James J. Corbett, MD Department of Neurology College of Medicine, University of Iowa Iowa City, Iowa [email protected]

Period prevalence and incidence of optic disc haemorrhage in normal tension glaucoma and primary open-angle glaucoma

To investigate and compare the period prevalences and incidences of optic disc haemorrhages in normal tension glaucoma and primary open-angle glaucoma. Hospital-based retrospective study. Four hundred and four patients with normal tension glaucoma and 210 patients with primary open-angle glaucoma that underwent consecutive disc examinations at least quarterly for at least 1 year and stereoscopic optic disc photographs at intervals of 6 to 12 months between 1992 and 2007. The period prevalence of disc haemorrhages, gender predominance among patients with disc haemorrhage, and cumulative incidence of normal tension glaucoma and primary open-angle glaucoma were compared. Period prevalence, cumulative incidence, and gender predominance of DHs in patients with NTG and POAG. Three hundred and eighty-seven patients (387 eyes) of normal tension glaucoma patients and 205 patients (205 eyes) of primary open-angle glaucoma patients were finally enrolled in the study. The period prevalence and incidence rates of the stereoscopic optic disc photograph-confirmed glaucomatous disc haemorrhages were 33.3% (129/387), 0.46 ± 0.18 times/year in the normal tension glaucoma group, and 17.6% (36/205), 0.34 ± 0.23 times/year in the primary open-angle glaucoma group, respectively. The absolute values and ratios of primary open-angle glaucoma and normal tension glaucoma in period prevalences and incidence rates in the present study were higher than in previous studies. No significant difference in gender ratios was found between patients that did or did not develop disc haemorrhage for both types of open-angle glaucoma (P > 0.05, respectively). The primary open-angle glaucoma group had higher period prevalences and incidence rates of disc haemorrhage than those reported previously. Disc haemorrhages were found to develop independent of gender.

Automated alternation flicker for the detection of optic disc haemorrhages

Optic disc haemorrhages are associated with active glaucomatous neurodegeneration and ongoing visual field loss. We sought to determine whether automated alternation flicker enhances the detection of disc haemorrhages in serial images from patients with glaucoma when compared to side-by-side photographic evaluation and single-image display. Serial sets of optic nerve photographs of 394 eyes from 234 patients followed for glaucoma at the authors' institutions were included in this study. Eyes with disc haemorrhages were graded for difficulty level and randomized along with nondisc haemorrhage control images into one of three presentation groups (automated alternation flicker, side-by-side or single image). Seven graders viewed all images and assessed for the presence or absence of disc haemorrhages. The sensitivity of automated alternation flicker for disc haemorrhage detection (0.878) was higher than side-by-side (0.705; p = 0.002) and single photographs (0.757; p = 0.01). There was no specificity difference between pairs of presentation groups (all p ≥ 0.7). Automated alternation flicker was a more sensitive method for disc haemorrhage detection than the current clinical standards and may have an important role in the management of glaucoma.

The Norfolk Island Eye Study (NIES): Rationale, Methodology and Distribution of Ocular Biometry (Biometry of the Bounty)

To describe the recruitment, ophthalmic examination methods and distribution of ocular biometry of participants in the Norfolk Island Eye Study, who were individuals descended from the English Bounty mutineers and their Polynesian wives. All 1,275 permanent residents of Norfolk Island aged over 15 years were invited to participate, including 602 individuals involved in a 2001 cardiovascular disease study. Participants completed a detailed questionnaire and underwent a comprehensive eye assessment including stereo disc and retinal photography, ocular coherence topography and conjunctival autofluorescence assessment. Additionally, blood or saliva was taken for DNA testing. 781 participants aged over 15 years were seen (54% female), comprising 61% of the permanent Island population. 343 people (43.9%) could trace their family history to the Pitcairn Islanders (Norfolk Island Pitcairn Pedigree). Mean anterior chamber depth was 3.32mm, mean axial length (AL) was 23.5mm, and mean central corneal thickness was 546 microns. There were no statistically significant differences in these characteristics between persons with and without Pitcairn Island ancestry. Mean intra-ocular pressure was lower in people with Pitcairn Island ancestry: 15.89mmHg compared to those without Pitcairn Island ancestry 16.49mmHg (P = .007). The mean keratometry value was lower in people with Pitcairn Island ancestry (43.22 vs. 43.52, P = .007). The corneas were flatter in people of Pitcairn ancestry but there was no corresponding difference in AL or refraction. Our study population is highly representative of the permanent population of Norfolk Island. Ocular biometry was similar to that of other white populations. Heritability estimates, linkage analysis and genome-wide studies will further elucidate the genetic determinants of chronic ocular diseases in this genetic isolate.

Glaucomatous optic neuropathy evaluation project: a standardized internet system for assessing skills in optic disc examination

Development of a standardized internet-based system to self-assess skills in optic disc examination for glaucoma risk assessment. Prospective internet-based observational study. Total of 197 participants (glaucoma subspecialists, general ophthalmologists and trainees) from 22 countries. Forty-two optic disc images demonstrating a range of features were selected from 2500 monoscopic disc photographs of normal and glaucomatous eyes. Images were presented to clinicians via website (http://www.gone-project.com). Participants were asked to assess nine topographic features and make a subjective assessment of glaucoma likelihood. Inter-observer agreement using kappa (κ) or weighted kappa (κ(w) ). There was substantial level of inter-observer agreement between glaucoma subspecialists for assessment of glaucoma likelihood (κ(w) = 0.63). Inter-observer agreement was high for haemorrhage (κ= 0.83) and substantial for disc size, disc shape, cup:disc ratio, peripapillary atrophy and cup shape (κ(w) = 0.59-0.68). Subspecialists had stronger inter-observer agreement for glaucoma likelihood and for most disc characteristics than did trainees: the greatest difference being the assessment for retinal nerve fibre layer loss. Analysis of individual disc answers from ophthalmology trainees showed that discs leading to lower agreement of glaucoma likelihood tend to produce lower agreement for the assessment of cup:disc ratio, cup shape, cup depth and retinal nerve fibre layer. Discs with features of moderate to deep cup or cup:disc ratio between 0.6 and 0.8 also lead to lower agreement in glaucoma likelihood. This internet-based system is a readily accessible and standardized tool, for clinicians globally, that permits self-assessment and benchmarking of skills in optic disc examination.

Assessment of rates of structural change in glaucoma using imaging technologies

To review the ability of current imaging technologies to provide estimates of rates of structural change in glaucoma patients. Review of literature. Imaging technologies, such as confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT), provide quantifiable and reproducible measurements of the optic disc and parapapillary retinal nerve fibre layer (RNFL). Rates of change as quantified by the rim area (RA) (for CSLO) and RNFL thickness (for SLP and OCT) are related to glaucoma progression as detected by conventional methods (eg, visual fields and optic disc photography). Evidence shows that rates of RNFL and RA loss are significantly faster in progressing compared with non-progressing glaucoma patients. Measurements of rates of optic disc and RNFL change are becoming increasingly precise and individualized. Currently available imaging technologies have the ability to detect and quantify progression in glaucoma, and their measurements may be suitable end points in glaucoma clinical trials.

Optic Disc Pit with Peripapillary Retinoschisis Presenting as a Localized Retinal Nerve Fiber Layer Defect

A 59-year-old woman was referred to our clinic for a glaucoma evaluation. The visual acuity and intraocular pressure were normal in both eyes. However, red-free fundus photography in the left eye showed a superotemporal wedge-shaped retinal nerve fiber layer defect, and visual field testing showed a corresponding partial arcuate scotoma. In an optical coherence tomography examination, the macula was flat, but an arcuate-shaped peripapillary retinoschisis was found. Further, the retinoschisis seemed to be connected with a superotemporal optic pit shown in a disc photograph. After 3 months of a topical prostaglandin analogue medication, the intraocular pressure in the retinoschisis eye was lowered from 14 to 10 mmHg and the peripapillary retinoschisis was almost resolved. We report a rare case of an optic disc pit with peripapillary retinoschisis presenting as a localized retinal nerve fiber layer defect.

Quantitative Analysis of Optic Disc Color

PurposeTo evaluate the reproducibility of ImageJ software in analyzing the color of the optic disc.MethodsOne hundred twelve normal participants (56 males and 56 females) were enrolled in this study. The image of the optic disc was taken using Kowa digital disc photo-graphy, and the gray scales of the nasal rim (NR), brightest cupping center (BCC) and largest inferior retinal vein (IRV) were calculated using histogram in ImageJ. Three different observers calculated the gray scales three separate times. Reproducibility was assessed using the interclass correlation coefficient (ICC).ResultsThe mean age of the participants was 50.6 years old (range, 11 to 82 years). The mean gray scales of the nasal rim were 91.81, 94.91, and 93.24; those of the brightest cupping center were 174.84, 179.94, and 177.76; and those of the largest inferior retinal vein were 61.85, 53.48, and 56.73 for observers 1, 2, and 3, respectively. Inter-observer reproducibility for NR, BCC and IRV was considered good based upon ICC values of 0.944, 0.860, and 0.789 for observers 1, 2, and 3, respectively. Significant age-related differences between the values of the brightest cupping center were noted, and the gray scale score was decreased in the older participants (p < 0.001).ConclusionsThe gray scale of the brightest cupping center diminished with age. ImageJ can be a useful objective tool with high reproducibility in the analysis of optic disc color.

Optic Disc Evaluation in Optic Neuropathies: The Optic Disc Assessment Project

Optic nerve morphology is affected by genetic and acquired disease. Glaucoma is the most common optic neuropathy; autosomal-dominant optic atrophy (ADOA) and Leber's hereditary optic neuropathy (LHON) are the most prevalent hereditary optic neuropathies. These 3 entities can exhibit similar topographical changes at the optic nerve head. Both ADOA and LHON have been reported to be misdiagnosed as glaucoma. Our aim was to determine whether glaucoma subspecialists and neuro-ophthalmologists can distinguish these diagnoses on optic disc assessment alone. Observational study. Twenty-three optic nerve experts. We randomized and masked 60 high-resolution stereoscopic optic disc photographs (15 ADOA images, 15 LHON, 15 glaucoma, and 15 normal controls). Experts were asked to assess the discs on 12 conventional topographic features and assign a presumptive diagnosis. Intra- and interanalysis was performed using the index of qualitative variation and absolute deviation. Can glaucoma specialists and neuro-ophthalmologists distinguish among the disease entities by optic nerve head phenotype. The correct diagnosis was identified in 85%, 75%, 27%, and 16% of the normal, glaucoma, ADOA, and LHON disc groups, respectively. The proportion of correct diagnoses within the ADOA and LHON groups was significantly lower than both normal and glaucomatous (P<0.001). Where glaucoma was chosen as the most likely diagnosis, 61% were glaucomatous, 34% were pathologic but nonglaucomatous discs, and 5% were normal. There was greater agreement for individual parameters assessed within the normal disc set when compared with pathologic discs (P<0.05). The only parameter to have a significantly greater agreement within the glaucomatous disc set when compared with ADOA or LHON disc sets was pallor, whereby experts agreed on is absence in the glaucomatous discs but were not in agreement on its presence or its absence in the ADOA and LHON discs (P<0.01). Optic neuropathies can result in similar topographic changes at the optic disc, particularly in late-stage disease, making it difficult to differentiate ADOA and LHON from glaucoma based on disc assessment alone. Other clinical parameters such as acuity, color vision, history of visual loss, and family history are required to make an accurate diagnosis.

Agreement Among 3 Methods of Optic Disc Diameter Measurement

To assess the agreement among clinical, Heidelberg Retina Tomograph (HRT), and optic disc photography in the optic disc diameter measurement. Prospective, observational study of 55 eyes of 55 subjects who underwent horizontal and vertical optic disc diameter measurements with +90 diopter lens on slit-lamp biomicroscopy (clinical) and on HRT and optic disc photography. Measurements were compared and agreement among the methods was assessed using intraclass correlation coefficients and Bland and Altman plots. Mean vertical diameter measured by clinical (1.93±0.28 mm) and on disc photography (1.9±0.22 mm) were comparable (P=0.812) and both were significantly greater (P<0.0001) than that measured on HRT (1.69±0.20 mm). Mean horizontal diameter by clinical (1.82±0.19 mm) and on disc photography (1.79±0.22 mm) were comparable (P=0.789) and both were significantly greater (P<0.01) than that measured on HRT (1.66±0.16 mm). The 95% limits of agreement on Bland and Altman plots ranged from 0.54 mm (clinical and disc photography) to 0.93 mm (clinical and HRT) for vertical diameter measurements and from 0.51 mm (HRT and disc photography) to 0.63 mm (clinical and HRT) for horizontal diameter measurements. Proportional bias was detected in the agreement between clinical and HRT as well as clinical and disc photography in vertical disc diameter measurement. Agreement between clinical and disc photography for optic disc diameter is better than that between either of these 2 methods and HRT. With the increasing disc size, there is an increasing disagreement in the vertical disc diameter measurements between the clinical and HRT as well as clinical and disc photography.

Three-dimensional Nature of Retinal Nerve Fiber Layer Defects

To demonstrate the 3-dimensional nature of wedge-shaped retinal nerve fiber layer (RNFL) losses. To study the impact of training glaucoma fellows in this identification technique by evaluating their rate of RNFL loss detection on stereo disc photographs. Wedge-shaped RNFL defects were identified in stereo disc photographs of early-glaucoma patients. The 3-dimensional nature of RNFL defects and overlying retinal blood vessel contour changes were identified. Four glaucoma fellows were given stereophotographs to identify the presence or absence of RNFL defects. After training in identification of RNFL defects by noting their 3-dimensional nature and overlying blood vessel contour changes, the same set of photographs were reevaluated by the fellows. We determined whether there was a difference between the before and after assessments in the probability of a correct response for each of the fellows. Loss of retinal thickness in the form of grooves and the resulting 3-dimensional nature of the RNFL defects were visualized on stereoscopic examination. Overlying retinal blood vessels coursed into and out of the RNFL defects. Three case examples of such wedge-shaped RNFL defects are presented. For each fellow, the proportion of RNFL defects correctly identified after training was greater than the proportion before training (P<0.001). Identifying the 3-dimensional nature of wedge-shaped RNFL defects may improve rate of detection of RNFL defects during clinical examination.

Internet‐based assessment of medical students’ ophthalmoscopy skills

Ophthalmoscopy is an important skill in undergraduate medical education. The use and outcome of a novel Internet-based method for assessing motor skills-related aspects of ophthalmoscopy skills in medical students are described. A total of 139 students in Malmö and 255 students in Umeå were assessed during four consecutive semesters. An optic disc photograph was obtained in each student. At assessment each student was asked to examine the eye of a fellow student. Fifteen disc photographs were displayed on a computer screen. One of the photographs was from the fellow student. The remaining images had been randomly selected. The student was asked to identify the optic disc of the fellow student from the 15 photographs on the screen. In one semester, the time spent on this by each student was recorded. All students completed the task. The average pass ratio was 96.4% (ranging from 94.0% to 98.0%). Median student times were 5.53 mins in Malmö and 6.36 mins in Umeå. This is the first automated, Internet-based assessment of an ophthalmic motor skill performed in co-operation between universities. The method used bears more similarities to real-life ophthalmoscopy than methods that use model eyes. Time investments and infrastructure demands were comparatively low. The method was designed for stand-alone assessment of ophthalmoscopy or as an objective structured clinical examination station, but it may also be used during the learning process. The collaboration between universities was easily transformed into routine practice and similar projects should be encouraged to increase the standardization of assessment.

Definition of high myopia by parapapillary atrophy. The Beijing Eye Study

Definition of high myopia by parapapillary atrophy. The Beijing Eye Study

Agreement and Accuracy of Non-Expert Ophthalmologists in Assessing Glaucomatous Changes in Serial Stereo Optic Disc Photographs

To compare the interobserver agreement in detecting glaucomatous optic disc changes using serial stereophotography between a large group of non-expert ophthalmologists and glaucoma specialists; to assess the accuracy of non-experts; to investigate whether the interobserver agreement and the accuracy of non-experts changed after a training session. Masked interobserver agreement study. Serial optic disc stereophotos from 40 patients with glaucoma. Three independent experienced glaucoma specialists (readers of the European Glaucoma Prevention Study) evaluated a set of 2 serial optic disc color stereo-slides for glaucomatous change, obtained with a delay varying from 2 to 7 years of 40 patients, masked from the temporal sequence of the slides. Each patient was graded as changed or stable by agreement of 2 of 3 of the experts (the reference standard). Thirty-seven non-expert ophthalmologists independently evaluated the same set of serial optic disc stereo-slides twice, with the second evaluation on the same day, masked from the results of the previous evaluation, after a training session on a separate slide set. Interobserver agreement of non-experts and experts in detecting glaucomatous optic disc changes (expressed as kappa coefficient); agreement of non-experts with the reference standard (accuracy) before and after a training session. The interobserver kappa coefficient (κ) of the non-experts and experts was 0.20 (95% confidence interval [CI], 0.19-0.21) and 0.51 (95% CI, 0.33-0.69), respectively (P<0.0001). The mean κ of the non-experts with the reference standard was 0.33 (95% CI, 0.27-0.39). After a training session, the interobserver agreement of the non-experts increased from 0.20 to 0.27 (95% CI, 0.26-0.28) (P<0.0001). The percentage agreement of the non-experts with the reference standard improved from 68.5% before to 71.4% after the training session (Wilcoxon signed-rank test, P=0.034). The interobserver agreement of non-expert ophthalmologists in detecting glaucomatous optic disc changes using serial stereophotos was significantly lower than that of experts, which was moderate. After a training session, the interobserver agreement and the accuracy of the non-experts showed a small but statistically significant improvement.

Keratoconus and Normal-Tension Glaucoma: A Study of the Possible Association With Abnormal Biomechanical Properties as Measured by Corneal Hysteresis

To test the hypothesis that patients with keratoconus and pellucid who have glaucoma or are glaucoma suspects have lower corneal hysteresis (CH) and/or corneal resistance factor (CRF) measurements compared with controls. A prospective study at a tertiary eye center of patients with keratoconus and pellucid, with glaucoma or suspect glaucoma and age-matched keratoconus and pellucid controls, was performed. After informed consent was obtained, corneal topography, ocular response analyzer (ORA; Reicher, Buffalo, NY), pachymetry, intraocular pressure, A scan measurements, Humphrey visual fields (VFs), and disk photographs were done. Analyses compared cases with controls on primary (CH and CRF) and secondary variables. Disk photographs and VFs were rated in a masked fashion. The mean CH [8.2 (SD = 1.6) and 8.3 (SD = 1.5)] and CRF [7.3 (SD = 2.0) and 6.9 (SD = 2.1)] were low and did not differ significantly between 20 study (29 eyes) and 40 control patients (61 eyes), respectively. CH had a negative significant correlation with maximum corneal curvature by topography (P < 0.002) and positive significant correlation with central corneal thickness (P < 0.003). The mean cup to disk ratio was larger (0.54, SD = 0.20) among cases than in controls (0.38, SD = 0.20), P = 0.003. VFs were suspicious for glaucoma more often among the study eyes (11 of 29, 33.9%) than controls (8 of 60, 13.3%), P = 0.019. CH was low in study and control patients and was correlated with severity of keratoconus/pellucid but not with glaucoma/glaucoma suspect or control status. Evidence of glaucoma was more common in study eyes than in controls but was present in both.

Diagnostic Accuracy of the Heidelberg Retina Tomograph for Glaucoma: A Population-Based Assessment

To evaluate the Heidelberg Retina Tomograph II (HRTII; Heidelberg Engineering, Heidelberg, Germany) as a screening tool for open-angle glaucoma (OAG) in an older population. Population-based, cross-sectional study. Participants from the 10-year follow-up Blue Mountains Eye Study (n = 1952; 75.6% of survivors). Participants underwent optic nerve head imaging performed using the HRTII; OAG was diagnosed independently from optic disc photographs and Humphrey 24-2 visual fields. The Moorfields Regression Analysis (MRA) was applied to scans using the default results of "normal," borderline," and "outside normal limits." Outcome classification was at the person level and used data from both eyes. Mean age was 73.7 years. The HRT scans could be acquired in 1644 participants, 95.9% of those fully examined; 87.4% of scans having a topography standard deviation (TSD) < or =40 microm. Larger TSD was associated with older age and OAG. The MRA sensitivity was 64.1%, specificity 85.7%, positive predictive value 21%, and negative predictive value 97.6% for detecting OAG. Including borderline results improved sensitivity (87.0%) but specificity dropped to 70.6%. Significant predictors of abnormal MRA included OAG (odds ratio [OR], 7.70; 95% confidence interval [CI] 4.79-12.35), age (OR, 1.05; 95% CI, 1.03-1.07), TSD (OR, 1.01; 95% CI, 1.003-1.020) and disc size (OR, 3.2; 95% CI, 2.31-4.49). Diagnostic accuracy was improved by restricting TSD <40 microm. Further TSD restriction improved specificity at the expense of sensitivity. As disc size increased, specificity fell whereas sensitivity, OAG prevalence, and the proportion testing positive rose. Glaucoma prevalence, positive predictive value, and the proportion testing positive increased, but specificity fell with increasing age. Sensitivity also fell between youngest and oldest groups. Diagnostic performance improved for visual field mean deviation < -4.0 dB. Single eye analyses overestimated specificity and underestimated sensitivity compared with using data from both eyes. Diagnostic test evaluation studies of HRTII using single eye analyses or restrictive selection overestimate test accuracy compared with this population-based study. Although the specificity of the MRA was inadequate for use as a glaucoma screening test, the HRTII performed relatively well in an unselected older population with acceptable quality scans in most eyes.

Effect of Optic Nerve Sheath Fenestration on Papilledema of the Operated and the Contralateral Nonoperated Eyes in Idiopathic Intracranial Hypertension

To evaluate the effect of optic nerve sheath fenestration (ONSF) on papilledema grade in the operated eyes and the contralateral nonoperated fellow eyes in patients with idiopathic intracranial hypertension (IIH). Retrospective review. A total of 78 patients underwent ONSF, and 20 patients served as controls. Charts of patients with IIH who had ONSF at the University of Iowa Hospital and Clinics were reviewed for age, gender, body mass index, and clinical findings. Optic disc photographs were graded by a masked observer using the Frisén papilledema grading scale at preoperative baseline and postoperatively at 2 weeks, 3 months, 6 months, and 12 months follow-up. Wilcoxon signed-rank test was used to examine the change in papilledema grade in both operated and nonoperated eyes at each time point. Grade of papilledema. Sixty-two patients (52 women and 10 men) with a mean age of 32 years (range, 13-57 years) underwent unilateral ONSF. The median grade of papilledema for operated and nonoperated eyes was 3 and 2, respectively, at preoperative baseline. Postoperatively the grade was 2 in each eye at 2 weeks (P<0.0001 and <0.0002 for operated and nonoperated eyes, respectively), 1 in each eye at 3 months (P<0.0001 for both operated and nonoperated eyes), 1 in each eye at 6 months (P<0.0001 for both operated and nonoperated eyes), and 0.5 and 1 for operated and nonoperated eyes, respectively, at 12 months follow-up (P<0.0001 for both operated and nonoperated eyes). There was no significant difference in grade of disc edema or reduction of disc edema on the basis of age, gender, or body mass index. Unilateral ONSF significantly decreases the grade of papilledema in both ipsilateral (operated) and contralateral (unoperated) eyes. The reduction of the papilledema and the stability of visual field in the contralateral (nonoperated) eyes suggest that bilateral ONSF may not always be necessary in patients with bilateral visual loss and papilledema due to IIH.

Lens opacity and refractive influences on the measurement of retinal vascular fractal dimension

To examine the influence of lens opacity and refraction on the measurement of retinal vascular fractal dimension (Df). Optic disc photographs (right eyes) of 3654 baseline Blue Mountains Eye Study participants (aged 49-97) were digitized. Retinal vascular Df was quantified using a computer-based program. Summated severity scores for nuclear, cortical and posterior subcapsular (PSC) cataract were assessed from lens photographs. Refraction data were converted to spherical equivalent refraction (SER), as sum spherical plus 0.5 cylinder power. Axial length was measured at 10-year follow-up examinations using an IOL master. Mean Df of the retinal vasculature was 1.444±0.023 for 2859 eligible participants. Increasing lens opacity scores were associated with significant reduction in Df (β=-0.0030, p<0.0001). Both cortical and PSC cataract involving central lens area were associated with reduced Df, after controlling for confounding factors (p(trend) ≤0.0105). Increasing myopia severity was associated with reduced Df after adjusting for lens opacity scores and other confounders (p(trend) <0.0001). The slope of Df decrease per SER reduction was 0.0040 in eyes with SER≤-4D, compared to -0.0016 in eyes with SER>-4D. For axial length quintiles, there were no significant differences in mean Df in all groups except a reduction in the fifth quintile (axial length ≥24.15mm) (all p<0.05). Ocular media opacity independently influenced retinal vascular Df measurement, but we found no evidence supporting any refractive axial magnification effect on this measure. Myopic refraction ≤-4D was associated with a reduction in Df, suggesting rarefaction of retinal vasculature associated with high myopia.

The relationship between the cornea and the optic disc

To evaluate the structural relationship between the cornea and the optic disc in normal subjects. This hospital-based observational study included 205 eyes from 205 individuals who were diagnosed as normal at our glaucoma clinic. The subjects underwent an eye examination, optic disc imaging with optic disc photography, optical coherence tomography, IOL master, specular microscopy, and ultrasound corneal pachymetry. In univariate regression models (Pearson's correlation coefficient), the cup-to-disc (CD) ratio showed a negative correlation with corneal curvature (r=-0.315, P<0.001) and central corneal thickness (r=-0.206, P=0.005), and a positive correlation with white-to-white diameter (horizontal limbus to limbus distance, r=0.215, P=0.003). In multiple linear regression models with CD ratio as the dependant parameter, the CD ratio was still significantly associated with corneal curvature (β=-0.205, P=0.011) and white-to-white diameter (β=0.207, P=0.010). The central corneal thickness failed to show statistical significance, but did show a negative correlation with borderline significance (β=-0.133, P=0.075). Eyes with a large CD ratio have large and flat corneas; this may suggest that there is a structural relationship between the cornea and the optic disc. These results can be helpful in analysing the anatomical relationship between the cornea and the optic disc.

Bilateral Ischemic Optic Neuropathy in a Patient Using Tacrolimus (FK506) After Liver Transplantation

The relationship between various kinds of optic neuropathy and drugs including amiodarone, ethambutol, linezolid, sildenafil, and interferon is reported in the literature (1). Tacrolimus (FK506, Prograf; Fujisawa USA, Inc., Deerfield, IL)-induced optic neuropathy was reported in three case reports; however, the mechanism of neurotoxicity is unclear (2–4). We report a case of bilateral ischemic optic neuropathy in the patient using tacrolimus and suggest the mechanism of tacrolimus neurotoxicity. A 54-year-old male patient was referred with a 10-day history of painless decreased vision in the left eye. The patient had liver cirrhosis associated with hepatitis B virus infection and had undergone liver transplantation 6 months before. The patient did not have any vascular risk factors. At the presentation, he was receiving mycophenolate 250 mg two times per day, prednisolone 2 mg four times per day, and tacrolimus 2.5 mg two times per day orally to maintain immunosuppression for 5 months. The best corrected visual acuity at the first examination was 20/20 OD and 20/400 OS. Relative afferent pupillary defect was noted in the left eye. The anterior segment and the fundus examination were normal. Cecocentral scotoma with an inferior predilection was revealed in Goldmann visual field (GVF) test, and delayed P100 latency was revealed in visual-evoked potential in the left eye. Laboratory study results including coagulation test were normal, whereas the results of blood studies for cytomegalovirus and mycobacteria were negative. At this time, tacrolimus and mycophenolate plasmatic levels were 6.2 and 1.3 mg/L, respectively. Brain magnetic resonance imaging was normal. Initially, we suspected an idiopathic ischemic optic neuropathy and planned regular follow-up. Three months later, his visual acuity of the right eye was also decreased to counting fingers and relative afferent pupillary defect was noted in the left eye. Visual acuity was counting fingers OS. Fundus examination was normal in the right eye; however, temporal pallor of optic disc was noted in the left eye (Fig. 1A). GVF test revealed cecocentral scotoma with an inferior predilection in both the eyes. Fluorescein angiography (FA) demonstrated no fluorescence filling in the optic disc in both the eyes, from the early phase to the late phase (Fig. 1B).FIGURE 1.: (A) Optic disc photograph at presentation of the right and the left eye shows normal appearance in the right eye and temporal pallor in the left eye. (B) Late-phase fluorescein angiography of the right and the left eye when the visual acuity in the right eye was decreased. There was no fluorescence filling in the optic disc in both eyes.We suspected ischemic optic neuropathy associated with tacrolimus and recommended to the general surgery department to discontinue tacrolimus medication. At this time, there was a mild increase in liver enzymes, and chronic rejection was suspected. Tacrolimus was immediately discontinued, instead cyclosporine was started for immunosuppression. Two weeks later, visual acuity had improved to 20/60 in the right eye but was still limited to counting fingers in the left eye. One month after discontinuing the medication, visual acuity was improved to 20/50 OD and stationary OS. GVF test revealed improved visual field in the right eye and stationary in the left eye, but FA revealed no fluorescence filling in the optic disc in both the eyes. At this time, cyclosporine plasmatic level was 100.9 ng/mL. Optic neuropathy associated with tacrolimus has been reported in three literatures (2–4). Two cases were bilateral (2, 4) and the other case was not clear in bilaterality, because the left eye was already blind secondary to retinopathy (3). There was an improvement in the visual acuity after discontinuing tacrolimus in two patients (2, 3). Optic disc edema was demonstrated in one patient (2). In these previous reports, mechanism of the optic neuropathy was unclear and suggested to be ischemia or direct neurotoxic effect and corroborative evidence was not provided. In this study, absolutely no blood flow to the optic disc was evident according to the FA results, suggesting that tacrolimus-induced ischemia might be one of the mechanisms of optic neuropathy. In the previous case reports, tacrolimus was believed to cause vasoconstriction and tissue ischemia through direct neurotoxic effect and vascular mechanism, similar to cyclosporine (2). In this case, tacrolimus was discontinued, but instead of tacrolimus, cyclosporine was started because of suspected chronic rejection. Later, the visual acuity of the patient was improved even using cyclosporine. Therefore, pathogenesis of tacrolimus-induced optic neuropathy may be different from cyclosporine-induced optic neuropathy. Different individual sensitivity to the neurotoxic and ischemic effect of tacrolimus and cyclosproine on optic nerve is another possibility. Tacrolimus is used in patients who undergo liver transplantation. In the case of decreased vision in patients receiving tacrolimus, the possibility of tacrolimus-induced optic neuropathy should be considered. Jaeha Yun Kyung-Ah Park Sei Yeul Oh Department of Ophthalmology Samsung Medical Center Sungkyunkwan University Seoul, Korea