Optic Nerve Head Cupping Research Articles

Software-Assisted Optic Nerve Assessment for Glaucoma Tele-Screening

Increased optic nerve head (ONH) cup-to-disc ratio (CDR) may indicate glaucoma but evaluation needs to be performed by a trained examiner. This research assessed new software to calculate CDR from ONH images. Digital stereoscopic ONH images from 28 subjects acquired during screening using a nonmydriatic 45-degree camera with 8.2-Megapixel resolution (Canon, Tokyo, Japan) were analyzed by 3 individuals with different levels of ophthalmic training: glaucoma specialist (GS), an optometrist (OD), and trainees. Images were logged and accessed by raters masked to each other's evaluations. Images from two groups were included: normal-appearing ONH (Group 1) and confirmed glaucoma (Group 2). All images were captured in DICOM format. Images were evaluated on a 32-bit, 1,600 x 1,200-pixel resolution monitor. EyeScape software (v. 7.4, Synemed, Inc., Benicia, CA) was used for CDR analysis. Software CDR determination requires an operator to place ONH disc and cup contour lines. Once lines were placed, the software provided CDR calculations (range 0.00-1.00). A total of 84 ONH evaluations were analyzed. Overall CDR mean, standard deviation, standard error of the mean, and mean difference from GS CDR evaluations were determined. Reproducibility was similar for all operators. The trainee had a small, statistically significant greater CDR in group 1 and 2 evaluations. Evaluation of ONH images for CDR can be performed using EyeScape software, by individuals with different levels of ophthalmic training. Accurate determination of CDR is important in tele-screening for vision-threatening diseases, and can aid in identifying subjects with suspicious ONH in need of specialty eye care.

Spectral Domain Optical Coherence Tomography and Glaucoma

Glaucoma may be the second leading cause of blindness in the world, affecting about 60 million people globally.1,2 The true prevalence may be underestimated as up to half of patients with glaucoma are undiagnosed, and a large proportion of glaucoma patients who are eligible for registration as legally blind remain unregistered.3–7 Glaucoma is a characteristic optic neuropathy characterized by retinal ganglion cell death, which then leads to retinal nerve fiber layer (RNFL) thinning and optic nerve head (ONH) cupping. The most important risk factor is elevated intraocular pressure. Since these structural changes in the RNFL and ONH may result in irreversible visual field (VF) loss,8,9 the early diagnosis of glaucoma is vital for the early initiation of treatment that may stop or slow down further permanent vision loss. One reason why early diagnosis often does not occur is that patients are usually asymptomatic early in their disease. Another problem preventing early diagnosis is that the standard clinical methods for diagnosing glaucoma (ie, VF testing) can only diagnose glaucomatous vision loss after up to 40% of the nerve tissue is lost irreversibly.10–13 VF testing is also not an ideal method to diagnose glaucoma because these tests rely on not only the subjective test response of the patient but also the subjective interpretation of the physician. Because of the need to diagnose glaucoma not only earlier but also in a more objective manner, various imaging technologies have been developed over the past decade in an attempt to quantitatively analyze progressive glaucomatous structural changes, such as RNFL thinning and/or ONH cupping, both of which are known to precede clinically detectable VF defects. So far, there are 3 main commercially available imaging technologies that are used to image glaucomatous structural changes: confocal scanning laser ophthalmoscopy (CSLO) (Heidelberg Retina Tomograph—HRTII and III, Heidelberg Engineering, Germany), scanning laser polarimetry (SLP) (GDxVCC, Carl Zeiss Meditec Inc, Dublin, CA), and optical coherence tomography (OCT). We feel that spectral domain optical coherence tomography (SDOCT), also called Fourier domain OCT, has the greatest potential for imaging glaucomatous structural changes. Before describing SDOCT in more detail, we will describe the science as to why CSLO, SLP, and traditional time domain optical coherence tomography (TDOCT) have not been proven to be better than a complete eye examination (which includes VF testing and stereo disc photography).14,15

3-D Histomorphometry of the Normal and Early Glaucomatous Monkey Optic Nerve Head: Prelaminar Neural Tissues and Cupping

To introduce a three-dimensional (3-D) histomorphometric strategy for characterizing the connective tissue (laminar) and prelaminar neural tissue (prelaminar) components of optic nerve head (ONH) cupping in one bilaterally normal monkey and three monkeys with early experimental glaucoma (EG) in one eye. Trephined ONH and peripapillary sclera from both eyes of four monkeys were serially sectioned at either 3-mum thickness (three EG monkeys) or 1.5-microm thickness (the bilaterally normal monkey) with the embedded tissue block face stained and imaged after each cut. Digital section images were aligned and stacked to create a 3-D reconstruction of each ONH. Within 40 digital radial sagittal sections of each reconstruction, Bruch's membrane opening (BMO), the neural canal wall, and the anterior laminar surface were delineated by two delineators. The 80 BMO points were used to establish a BMO-zero reference plane. The parameters prelaminar tissue volume, post-BMO cup (the estimate of the clinical cup), and post-BMO total prelaminar volume (a global measure of ONH connective tissue deformation) were calculated overall and within 15 degrees radial regions. The parameter prelaminar tissue thickness was calculated at each delineated anterior laminar surface point. For each monkey, an intra-animal difference map was generated for each parameter. Overall volume and thickness data were compared between normal and EG eyes by analysis of variance (ANOVA). Regionally variable expansion of post-BMO cup volume and post-BMO total prelaminar volume were present in all three EG eyes and far exceeded the intra-animal, physiologic differences for these parameters in the bilaterally normal monkey. Prelaminar tissue thickness was increased in all three EG monkeys, with the greatest effects present within the peripheral regions of the canal. These data suggest that in young adult monkeys with more compliant connective tissues, clinical cupping in early glaucoma is primarily due to fixed deformation of the ONH connective tissues and occurs in the setting of prelaminar tissues that are thickened rather than thinned.

Effect of pupillary dilatation on glaucoma assessments using optical coherence tomography

Aims:To examine the effect of pupillary dilatation on the reliability of retinal nerve fibre layer (RNFL) and optic nerve head (ONH) assessments using Stratus OCT in a glaucoma clinic.Methods:Observational study...

Macular Schisis and Detachment Associated with Presumed Acquired Enlarged Optic Nerve Head Cups

To describe a clinical syndrome of macular schisis and detachment in patients with acquired optic nerve head cupping resulting from glaucoma. Retrospective review of five patients. Patients were included if they had optic nerve cupping and macular schisis with or without detachment with no other identifiable cause. The patients had to have no leakage on fluorescein angiography and no vitreous traction on examination or on optic coherence tomography (OCT). These patients were followed up and visual acuity, intraocular pressure, and the findings of serial fundus and OCT examinations were noted. Five patients had schisis with or without detachment of the macula with pronounced optic nerve head cupping. One patient had resolution of the macular fluid after filtering surgery for uncontrolled glaucoma. Two patients underwent a vitrectomy with intraocular gas and had almost total resolution of macular fluid and improved vision. Macular schisis and detachment can occur in patients with presumed enlarged optic nerve head cups in the absence of obvious congenital anomalies of the disk. The authors believe the cause is leakage of fluid from the vitreous through a tiny hole in the thin tissue of the cup. This is a similar mechanism to that seen in patients with optic pits. A vitrectomy or steps to reduce the intraocular pressure may result in resolution of the fluid and improved vision.

Familial Cavitary Optic Disk Anomalies: Clinical Features of a Large Family with Examples of Progressive Optic Nerve Head Cupping

To describe a multigenerational family with autosomal dominant inheritance of cavitary optic nerve head (ONH) anomalies and abnormal ONH vasculature. Description of a single family with inherited eye disease. A four-generation pedigree was investigated. Examination included visual acuity, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and ophthalmoscopy. Visual fields and fundus photography were obtained when possible. Seventeen clinically affected individuals and two obligate carriers were identified. Most (64.7%) affected persons had bilateral involvement. Visual acuity in affected eyes ranged from 20/20 to no light perception. Although the appearance of affected nerves varied greatly, most lacked a well-formed central retinal artery and instead had multiple radial cilioretinal arteries. Prominent cupping was seen in most affected nerves. Four individuals for whom information was available were treated for glaucoma, but none had documented elevated IOP. Four eyes of two patients demonstrated progressive ONH cupping at normal IOPs. Nine (56.3%) of the 16 individuals for whom we had data had evidence of serous macular detachments; five of these had bilateral macular disease. A large family with autosomal dominant inheritance of cavitary ONH anomalies and abnormal vasculature is presented. Clinical phenotypes varied markedly. Progressive ONH cupping was documented in four eyes of two patients. Genetic linkage analysis of this family has identified the chromosomal location of a gene responsible for ONH development. This may provide insight into the pathogenesis of glaucomatous ONH damage.

Assessment of change of optic nerve head cupping in pediatric glaucoma using the RetCam 120

To ascertain the interobserver agreement among various specialists when analyzing images of the optic nerve head taken with the RetCam 120 (Clarity Medical Systems, Inc., Pleasanton, CA) for assessing the progression of optic disk cupping in pediatric glaucoma. Five observers compared pairs of RetCam 120 two-dimensional photographs from 64 eyes to identify whether or not changes in the optic disk had occurred. Observers included a pediatric glaucoma specialist, pediatric neurophthalmologist, strabismologist, pediatric ophthalmic imaging specialist, and pediatric ophthalmology fellow. Each was masked to the patient identity and clinical course. For each patient, the observers reviewed the photographs taken prior to therapy and at a minimum of 6 months following initiation of therapy. Interobserver variability was calculated and analysis conducted to identify influential variables. Poor agreement was noted between the observers. No significant association was obtained between agreement level and variables affecting photographic quality: variability of contrast and illumination, exposure and magnification, image clarity, presence of fluorescein on the cornea, and pixelation of the image with poor resolution. Raters noted problems with these image variables in 75.6% of the observations. The Kappa statistic obtained was kappa = 0.29 with overall proportion of agreement of p = 0.69, suggesting a fair agreement but not a moderate agreement. Comparison of RetCam 120 pediatric optic nerve head photographs, when performed subjectively by observers with different perspectives, and in isolation from clinical information, may not be a reliable indicator of cupping change. In addition, variations in image contrast, luminance, color, and pixelation pose significant challenges to agreement between observers. Comparison of RetCam 120 images should not be considered the sole criterion for monitoring pediatric glaucoma.

OPHTHALMIC EXAMINATION OF THE CAPTIVE WESTERN LOWLAND GORILLA (GORILLA GORILLA GORILLA)

This study examined the captive western lowland gorilla (Gorilla gorilla gorilla) eye as compared and contrasted with the human eye. Bilateral ophthalmic examinations of western lowland gorillas (n = 5) while under general anesthesia were performed opportunistically, including slit-lamp biomicroscopy, dilated fundus examination, cycloplegic retinoscopy, Schiotz tonometry, corneal diameter and thickness measurements, A-scan and B-scan ultrasonography, keratometry, and cultures of the eyelid margins and bulbar conjunctiva. Mean spherical equivalent refractive error by cycloplegic retinoscopy was +1.20 +/- 0.59 diopters. Mean intraocular pressure by Schiotz tonometry was 12.0 +/- 4.3 mm Hg. Mean optic nerve head cup to disc ratio was 0.42 +/- 0.11. Mean horizontal corneal diameter was 13.4 +/- 0.8 mm, and mean vertical cornea diameter was 12.7 +/- 0.8 mm. Mean central corneal thickness by ultrasound pachymetry was 489 +/- 52 microm. Mean axial length of the eye by A-scan was 22.75 +/- 0.71 mm. Mean lens thickness by A-scan was 4.23 +/- 0.34 mm. Mean anterior chamber depth by A-scan was 4.00 +/- 0.26 mm. Mean keratometry reading was 44.38 +/- 1.64 diopters. Eyelid margin and bulbar conjunctival cultures isolated Candida sp. (n = 5), Staphylococcus aureus (n = 4), Staphylococcus epidermidis (n = 3), Staphylococcus saccharolyticus (n = 3), and Micrococcus sp. (n = 3). This study suggests important similarities between western lowland gorilla and human eyes. These similarities may allow diagnostics, techniques, and equipment for human eye surgery, such as those used for cataract extraction and intraocular lens implantation, to be successfully utilized for gorillas.

Canine ocular onchocerciasis in the United States: two new cases and a review of the literature

Since 1991, 53 cases of canine ocular onchocerciasis have been reported in the literature worldwide, 43 of these were from Greece, five from Hungary, and five from the western United States. Information on the histopathologic features of canine ocular onchocerciasis is limited. We describe the histopathologic features of canine ocular onchocerciasis in two dogs from California that presented clinically with firm episcleral nodules and uveitis unilaterally. Pertinent literature and pathogenesis are reviewed; recognizable clinical features and treatment are discussed. The cases presented were diagnosed via histopathology of the enucleated globes and episcleral granulomas at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Positive identification of adult Onchocerca within episcleral granulomas was made based on light-microscopy features. Histopathologic examination of both globes revealed episcleral parasites surrounded by granulomas containing few to moderate numbers of eosinophils. Other sequelae, in both cases, included lymphoplasmacytic uveitis, preiridal fibrovascular membranes, peripheral anterior synechiae, retinal degeneration, and optic nerve head cupping. Both male and female worms were present, as were in utero microfilariae in both cases. Worms in both cases were tentatively identified as Onchocerca lienalis. Ocular onchocerciasis should be a differential consideration in cases of canine conjunctival nodules or periorbital swelling, particularly in dogs from the western United States.

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

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

Diagnosis of glaucoma using telemedicine--the effect of compression on the evaluation of optic nerve head cup-disc ratio.

A photograph of the optic nerve head requires a lot of disk space (over 1 MByte) for storage and may require substantial bandwidth and time for transmission to a remote practitioner for a second opinion. To test whether compression degrades the image quality of the images, 302 slides were digitized at an optical resolution of 2400 pixels/inch (945 pixels/cm) and 30 bit/pixel. The images were saved both in non-compressed TIFF format and in compressed JPEG (compression ratio of 60) format. A blinded observer measured the optic nerve head cup-disc ratio for all three groups: the original slides, uncompressed TIFF and compressed JPEG images. The results showed that digital images were less accurate than slides. However, compression, even up to a ratio of 40, did not make matters worse.

Glaucoma and ocular hypertension in pediatric patients with cataracts

Background: The pathogenesis of open-angle glaucoma and ocular hypertension in patients who have undergone surgical correction of their congenital cataracts remains undetermined. This study examines the prevalence of glaucoma and ocular hypertension in a population of patients who did not undergo surgical correction of their pediatric cataracts. Methods: Fifty-eight eyes of 41 patients had cataracts before 2.5 years of age and were followed up until at least 5 years of age without operative correction. The patients were studied for the following parameters: age at diagnosis, type of cataract, etiology, bilaterality, optic nerve head cup-to-disc ratio, intraocular pressures, and reason why the patient did not undergo an operation. Glaucoma was defined as the presence of glaucomatous optic nerve head cupping with intraocular pressures of greater than 22 mm Hg. Ocular hypertension was defined as intraocular pressures greater than 22 mm Hg with no optic nerve changes. Results: Nine of the 58 eyes had cataracts caused by persistent hyperplastic primary vitreous. The average age to the last intraocular pressure measurement was 19 years (range 5 to 48 years). Closed-angle glaucoma developed in two patients with persistent hyperplastic primary vitreous. Neither open-angle glaucoma nor ocular hypertension developed in any patients. Conclusion: Pediatric cataracts not of the persistent hyperplastic primary vitreous type were not associated with ocular hypertension or glaucoma in the absence of surgical cataract correction. In eyes with persistent hyperplastic primary vitreous cataracts, spontaneous closed-angle glaucoma developed in two of nine patients and open-angle glaucoma developed in none. Surgical cataract correction, or the aphakic state that follows such operations, may be responsible for pediatric aphakic glaucoma.

The vascular concept of glaucoma

The regulation of ocular perfusion is different for different parts of the eye. Observations on the retina can, therefore, not be extrapolated to the optic nerve head. Extraocular vessels, especially the short posterior ciliary arteries, might play a major role in regulation of ocular circulation, but additional regulation takes place in the eye itself. Dysregulation might be transient and, thus, not necessarily present and detectable at any one examination. Older patients with arteriosclerotic vessels may behave differently in this regard than do young, healthy animals. Not only the arterial but also the venous side of the circulation may be disturbed. Disk hemorrhages can not only be a sign of damage; they can also provoke ischemia. Besides hypoxia, diseased vessel walls might play a direct role in the pathogenesis of optic nerve head cupping. Finally, a relation between vascular dysregulation and aqueous-humor dynamics is conceivable.

Optic Disk Cupping and Electrocardiographic Abnormalities in an American Pedigree with Leber's Hereditary Optic Neuropathy

We examined the clinical characteristics of affected and unaffected members of an American black family with the 11778 mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Thirty-six individuals from four generations were included. All maternally related subjects were shown to be essentially homoplasmic for the 11778 mitochondrial DNA mutation in blood. Paternally related subjects did not carry this mutation. Patients affected with optic neuropathy had optic nerve head cupping. Loss of unmyelinated axons from the prelaminar optic nerve may be responsible for cupping in these patients. Electrocardiographic analysis of subjects carrying the 11778 mitochondrial DNA mutation disclosed statistically significant (P = .02) prolongation of the corrected OT interval as compared to control subjects. While the clinical significance of this magnitude of corrected QT prolongation is unknown, it may represent a systemic manifestation of the 11778 mutation. No electrocardiographic evidence of preexcitation syndromes was seen.

Photogrammetric Analysis of Volume Asymmetry of the Optic Nerve Head Cup in Normal, Hypertensive, and Glaucomatous Eyes

Recent studies of optic cup volume, depth, and orifice area demonstrated a large overlap of the range of these factors for normal and glaucomatous eyes, suggesting that it is usually not possible to distinguish abnormal disks on the basis of a particualr set of geometric quantifiers. Because of the knowledge that qualitative asymmetry of a person's optic cups may be a sign of glaucoma, calculation of the quantity of cup asymmetry using the aforementioned geometric parameters was undertaken in 90 patients. Results indicated that 90% of the bilaterally normal subjects who were studied and 80% of the ocular hypertensives had less than 0.20 mm3 cup volume asymmetry. In contrast, however, all of the unilateral glaucoma patients in this sample exceeded that value. It therefore appears that measurement of the amount of, volume asymmetry between a person's optic cups may be a useful tool in the diagnosis of glaucoma.

ACUTE LUPUS ERYTHEMATOSUS

<h3>Aims:</h3> To examine the effect of pupillary dilatation on the reliability of retinal nerve fibre layer (RNFL) and optic nerve head (ONH) assessments using Stratus OCT in a glaucoma clinic. <h3>Methods:</h3> Observational study of 38 patients attending a glaucoma clinic. The “fast optic disc” and “fast RNFL thickness” programs on Stratus OCT were used to measure the RNFL thickness and ONH cup to disc ratio (CDR). Two scans were done before dilatation and two after dilatation with tropicamide 1% drops. The mean values and reproducibility before and after dilatation were compared, along with the quality of scans as indicated by the “signal strength” score. <h3>Results:</h3> In nine patients (23.7%) no images were obtained undilated but after dilatation examination was possible in all patients. Inability to obtain an undilated scan was associated with smaller pupil size and increasing cataract. The scan quality, as judged by the signal strength score, was higher dilated than undilated for both RNFL thickness (p = 0.011) and ONH CDR (p = 0.007). Reproducibility was higher with dilated scans for RNFL thickness but not for ONH CDR. There were significant differences between the dilated and undilated examinations for three of the five RNFL thickness variables and two of the three ONH CDR categories. <h3>Conclusions:</h3> Acquisition of high quality OCT images was not possible without pupillary dilatation in about 25% of the patients. The dilated scans were more reproducible and of higher quality than the undilated scans. The two methods of examination do not appear to be interchangeable, suggesting that in follow up examinations the pupil should be in the same condition as at baseline. Pupillary dilatation is recommended before glaucoma assessments using Stratus OCT.