Optic nerve axon number in mouse is regulated by PAX2.

BACKGROUND: Papillorenal syndrome is an autosomal-dominant disease caused by mutations in the PAX2 transcription factor gene. Patients often exhibit congenital excavation of the optic nerve and a spectrum of congenital kidney abnormalities. Using a novel mouse model of this syndrome (C57BL/6J PAX2(A220G/+)), we investigated the effect of PAX2 haploinsufficiency on optic nerve axon number. Because PAX2 expression and retinal pigment epithelium pigmentation have a mutually exclusive relationship during development and because tyrosinase (Tyr) has been shown to modify the penetrance of other ocular development genes, we also investigated whether tyrosinase modified the mutant PAX2 phenotype. METHODS: C57BL/6J PAX2(A220G/+)Tyr(+/+) mice were crossed with mice of the same genetic background (C57BL/6J) that are homozygous for an effective null allele of tyrosinase (Tyr(c-2J/c-2J)) over two generations to create mice with four distinct genotypes: PAX2(A220G/+) Tyr(+/c-2J), PAX2(A220G/+) Tyr(c-2J/c-2J), PAX2(+/+) Tyr(c-2J/+), and PAX2(+/+)Tyr(c-2J/c-2J). Mouse optic nerves were examined clinically and histologically. Axon number was assessed in a masked fashion in optic nerves from mice of all four genotypes and compared with parental strains. RESULTS: Mice heterozygous for a PAX2 mutation show reduced optic nerve axon number compared with age-matched controls. Tyrosinase does not appear to modify this phenotype. CONCLUSIONS: Our results show that PAX2 is important in determining axon number in mouse optic nerve. The developmental effects of tyrosinase and PAX2 mutation appear to act via different pathways.

Capsule staining as an adjunct to cataract surgery: a report from the American Academy of Ophthalmology.

OBJECTIVE: This document evaluates currently available data in the published literature to answer the question of whether the use of dye such as indocyanine green or trypan blue to stain the lens capsule to improve visualization is safe and effective as an adjunct to cataract surgery. METHODS: Literature searches conducted in March 2003 and May 2004 retrieved 139 citations. The panel members reviewed the abstracts and selected 47 of possible clinical relevance for review. An additional 14 articles were identified for evaluation. Of the 61 articles reviewed, the panel members selected 36 for the panel methodologist to review and rate according to the strength of the evidence. A level I rating was assigned to properly conducted, well-designed, randomized clinical trials; a level II rating was assigned to well-designed cohort and case-control studies; and a level III rating was assigned to case series and case reports. RESULTS: There is level III evidence that indocyanine green, trypan blue, and fluorescein are each effective in staining the lens capsule and that indocyanine green and trypan blue provide better ease of use and visualization of the capsule than fluoroscein. There is level II evidence that staining the capsule is helpful in completing capsulorrhexis and that it is helpful for pediatric patients under age 5 years and in cases of white cataract. The overall surgical advantage of a completed continuous curvilinear capsulorrhexis using dye has not been demonstrated, but this may be related to the outcome measures chosen rather than a failure to confer advantage. There are substantial data indicating that trypan blue 0.1% is not toxic to the cornea. There are limited data suggesting that indocyanine green 0.125% to 0.5% is not toxic to anterior segment structures. CONCLUSIONS: There are data confirming that dye is safe and effective as an adjunct for capsule visualization in cataract surgery. It is reasonable to use dye when inadequate capsule visualization may compromise the outcome in cataract surgery. More studies are needed to confirm a lack of toxicity of indocyanine green and trypan blue, particularly in the event of posterior segment or longer duration exposure.

Magnetic resonance angiography and clinical evaluation of third nerve palsies and posterior communicating artery aneurysms.

OBJECT: The authors conducted a study to determine the utility of the clinical profile and magnetic resonance (MR) angiography in evaluating patients with isolated third cranial nerve palsies or posterior communicating artery (PCoA) aneurysms. METHODS: Three-dimensional time-of-flight MR angiography was performed in a consecutive series of patients with isolated acute third cranial nerve palsy not due to a ruptured aneurysm and in patients with unruptured PCoA aneurysms. A neuroradiologist, masked to the identities of the patients, interpreted reformatted maximum intensity projection (MIP) and source images of the PCoAs and aneurysms. The investigators assessed clinical features of oculomotor nerve dysfunction and focal head pain. Cases involving cranial third nerve palsy without aneurysms were classified as Group 1 (no case entailed catheter-based angiography), and cases involving PCoA aneurysms seen on MR angiography (42 cases confirmed by catheter-based angiography) were classified as Group 2. The mean age of the 73 patients in Group 1 was 60.1 years and that of the 45 patients in Group 2 was 59.1 years (p = 0.37). The pattern and severity of oculomotor (p = 0.61) and lid (p = 0.83) dysfunction and pain frequency (p = 0.2) were similar for the 73 patients with vasculopathy in Group 1 and the 15 symptomatic patients in Group 2. Abnormal pupils were observed in 38% of the patients in Group 1 and 80% of those in Group 2 (p = 0.016). In cases of complete external third nerve palsy, nine of 22 in Group 1 and none of four in Group 2 had normal pupil function. For all patients, source imaging showed 206 PCoAs (85%) and MIP imaging demonstrated 120 PCoAs (49%). Of 48 aneurysms (three bilateral), MIP imaging showed 44 (92%) and source imaging showed 47 (98%). Only a 2-mm aneurysm seen on catheter-based angiography was missed by MR angiography. Symptomatic aneurysms were equal or greater than 4 mm in size. CONCLUSIONS: Only the presence of complete external third nerve palsy and normal pupil function allowed ischemia to be clinically distinguished from a PCoA aneurysm in a patient with isolated third nerve palsy and no subarachnoid hemorrhage. When source image MR angiography demonstrates normal findings, catheter-based angiography need not be performed in these patients, even if pupil function is abnormal.

Are patients with social developmental disorders prosopagnosic? Perceptual heterogeneity in the Asperger and socio-emotional processing disorders.

It has been hypothesized that social developmental disorders (SDD) like autism, Asperger's disorder and the social-emotional processing disorder may be associated with prosopagnosic-like deficits in face recognition. We studied the ability to recognize famous faces in 24 adults with a variety of SDD diagnoses. We also measured their ability to discriminate changes in internal facial configuration, a perceptual function that is important in face recognition, and their imagery for famous faces, an index of their facial memory stores. We contrasted their performance with both healthy subjects and prosopagnosic patients. We also performed a cluster analysis of the SDD patients. One group of eight SDD subjects performed normally on all tests of face perception and recognition. The other 16 subjects were impaired in recognition, though most were better than prosopagnosic patients. One impaired SDD subgroup had poor perception of facial structure but relatively preserved imagery, resembling prosopagnosic patients with medial occipitotemporal lesions. Another subgroup had better perception than imagery, resembling one prosopagnosic with bilateral anterior temporal lesions. Overall, SDD subgroup membership by face recognition did not correlate with a particular SDD diagnosis or subjective ratings of social impairment. We conclude that the social disturbance in SDD does not invariably lead to impaired face recognition. Abnormal face recognition in some SDD subjects is related to impaired perception of facial structure in a manner suggestive of occipitotemporal dysfunction. Heterogeneity in the perceptual processing of faces may imply pathogenetic heterogeneity, with important implications for genetic and rehabilitative studies of SDD.

Encapsulated cell-based intraocular delivery of ciliary neurotrophic factor in normal rabbit: dose-dependent effects on ERG and retinal histology.

PURPOSE: ERG and histologic changes were investigated in normal rabbits after intravitreal implantation of encapsulated cell technology (ECT) devices releasing ciliary neurotrophic factor (CNTF). METHODS: Fifteen adult New Zealand White albino rabbits had ECT devices secreting CNTF at 22, 5, or 0 ng/d implanted in the superior temporal quadrant of the left eye. The low dose has been shown to produce substantial rescue of photoreceptors in the rcd1 canine model of retinal degeneration. Right eyes were untreated. Ganzfeld dark- and light-adapted ERGs and clinical observations were performed at 5, 15, and 25 days after implantation. Rod a-waves and rod and cone b-waves and outer nuclear layer (ONL) morphology were evaluated at 25 days. RESULTS: Clinical examination showed minimal changes in a few CNTF-treated eyes, including vitreous membranes and engorgement of iris vessels at day 25. Retinas appeared normal. CNTF did not significantly affect the rod a- or b-waves, although the b-wave amplitude tended to be larger in CNTF-treated retinas at low flash intensities. The cone b-wave amplitude was significantly reduced in high-dose eyes at some flash intensities. The ONL area in high-dose eyes was significantly greater because of increased thickness than in fellow retinas. ONL cell size was significantly increased, and staining density decreased in CNTF-treated retinas. CONCLUSIONS: CNTF, given by intravitreal ECT device at doses that protect photoreceptors in a canine model of retinal degeneration (5 ng/d), did not adversely affect either rod or cone ERG function of normal rabbit retina. The cone ERG was more sensitive to suppression being reduced, at low flash intensities, by 22 ng/d. Dose-related changes in the ONL and photoreceptor cell nuclei did not represent a toxic effect, because they were not associated with deficits in the rod ERG over a broad range of intensities.

Effects of aldose reductase inhibitors and galactose withdrawal on fluorescein angiographic lesions in galactose-fed dogs.

OBJECTIVE: To assess the effect of aldose reductase inhibitor (ARI) M79175 (2-methyl-6-fluoro-spiro-chroman-4-5'-imidazolidine-2',4'-dione) administration and galactose withdrawal on the progression of retinal changes using fluorescein angiography in galactose-fed dogs. METHODS: Thirty male beagles were randomized into 4 groups. Three dogs were fed a normal control diet containing 30% nonnutritive fiber for 74 months (control group), 11 dogs a 30% galactose diet for 74 months (continuous galactose group), 8 dogs a 30% galactose diet for 36 months followed by replacement with a normal diet for 36 months (galactose withdrawal group), and 8 dogs a 30% galactose diet supplemented with M79175 for 34 months followed by replacement with a normal diet and removal of M79175 treatment for 38 months (ARI-treated galactose withdrawal group). Stereoscopic color fundus photography and fluorescein angiography, performed at baseline and follow-up, were assessed for the clinical development of retinopathy, including the first appearance of hyperfluorescence, varying severity of retinal nonperfusion, and retinal neovascularization. Histopathologic features were examined in selected dogs. RESULTS: All dogs in the 3 groups fed the 30% galactose diet developed areas of hyperfluorescence and nonperfusion. Of these dogs, only those supplemented with the ARI did not develop areas of nonperfusion greater than or equal to half the field and retinal neovascularization. Parametric survival analysis showed significant differences (galactose withdrawal group vs ARI-treated galactose withdrawal group) in the median times to the development of nonperfusion greater than or equal to half the field (P =.003) and retinal neovascularization (P =.03). CONCLUSION: Normalization of glycemic control with galactose withdrawal and ARI treatment may delay the onset and progression of retinal lesions in galactose-fed dogs. Clinical Relevance Perfect glycemic control after a period of poor control does not completely prevent the progression of retinal lesions. Therapy with ARIs may potentially be important in the prevention of retinal lesions associated with diabetic eye disease.

Tarsal-conjunctival disease associated with Wegener's granulomatosis.

OBJECTIVE: To describe the clinical characteristics of tarsal-conjunctival disease in a cohort of patients with Wegener's granulomatosis (WG). DESIGN: Retrospective, case-controlled study. PARTICIPANTS: The medical records of 82 consecutive WG patients who underwent an eye examination between January 1996 and June 2002 at the National Institutes of Health were reviewed. METHODS: Details of the ophthalmic examination, results of medical therapy, and histopathologic analysis results were recorded. Tarsal-conjunctival disease was defined by (1). conjunctival hyperemia and granuloma formation, areas of necrosis, or active fibrovascular changes in the tarsus or conjunctiva, or (2). evidence of inactive fibrovascular scar. The association of tarsal-conjunctival disease with major organ system involvement was assessed using Bayesian methods. MAIN OUTCOME MEASURES: The occurrence and clinical characteristics of tarsal-conjunctival disease in a cohort of patients with WG and associations with major organ system involvement. RESULTS: Tarsal-conjunctival disease occurred in 13 of 82 patients (16%) with WG examined over a 6.5-year period. The palpebral surface of the upper lid was involved most commonly, showing conjunctival hyperemia in seven patients, granulomatous lesions in three patients, tarsal-conjunctival necrosis in four patients, active fibrovascular proliferation in six patients, and inactive fibrous scar tissue in seven patients. Histopathologic analysis of eyelid biopsy specimens showed granulomatous inflammation, focal necrosis, and areas of occlusive vasculitis in the tarsus and conjunctiva. In reviewing the patterns of organ involvement in patients with and without tarsal-conjunctival disease, the association of subglottic stenosis and nasolacrimal duct obstruction with tarsal-conjunctival disease showed a high probability of clinical significance. CONCLUSIONS: Tarsal-conjunctival disease, a previously uncommon finding in patients with WG, was characterized by inflammation of the palpebral conjunctiva and tarsus followed by a fibrovascular proliferation and scar formation. Because of the important association of tarsal-conjunctival disease with subglottic stenosis, which can progress and lead to laryngeal obstruction and respiratory failure, patients with tarsal-conjunctival disease should be referred to an otolaryngologist for evaluation.

Vision-related quality of life in people with central retinal vein occlusion using the 25-item National Eye Institute Visual Function Questionnaire.

OBJECTIVE: To study visual function and vision-related quality of life in persons with central retinal vein occlusion using the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). METHODS: Interviewer-administered study of persons with central retinal vein occlusion. Scores on the VFQ-25 were analyzed and converted to a 100-point scale in which 100 represents the best possible score and 0 represents the worst. Subscale results were compared with previously published data, and a subgroup analysis was performed. RESULTS: Fifty-one patients participated. The mean adjusted subscale responses were significantly lower than those from a reference group of patients without ocular disease but not significantly different from patients with diabetic retinopathy. Responses to the VFQ-25 correlated most strongly with visual acuity in the better-seeing eye, number of systemic medical conditions, and patients' opinions about their general health. Responses did not correlate with visual acuity in the involved eye. CONCLUSIONS: Central retinal vein occlusion is an ocular disease that is associated with a decreased vision-related quality of life as measured by the VFQ-25. A decrease in VFQ-25 scores is related to the degree of visual loss in the better-seeing eye and the overall systemic health of the patient.

Intraocular lens implantation in the absence of capsular support: a report by the American Academy of Ophthalmology.

OBJECTIVE: This review was conducted to determine the safety and efficacy of open-loop anterior chamber, scleral-sutured posterior chamber, and iris-sutured posterior chamber intraocular lenses (IOLs) in eyes with inadequate capsular support for posterior chamber implantation in the capsular bag or ciliary sulcus. It also attempted to determine whether there is a preferred IOL or fixation site of choice in eyes with inadequate capsular support. METHODS: A literature search conducted for the years 1980 to 2001 yielded 189 citations related to IOL implantation in the absence of capsular support. An update search, conducted in March 2002, yielded an additional 28 articles. The Anterior Segment Panel members reviewed these abstracts and selected 148 articles of possible clinical relevance for review. Of these, 89 were considered sufficiently clinically relevant for the panel methodologist to review and rate according to the strength of evidence. A level I rating was assigned to properly conducted, well-designed, randomized clinical trials; a level II rating was assigned to well-designed cohort and case-control studies; and a level III rating was assigned to case series. Articles comparing the safety and efficacy of the IOL type and fixation site were further evaluated for the quality of the statistical methods used in the study. Studies with a rating of A or B were considered acceptable, C was borderline, and D and F were considered unacceptable as medical evidence. RESULTS: Forty-three articles with data concerning outcome of IOL insertion in eyes with inadequate capsular support had an evidence rating of level III or higher and were used in the final review of the safety and efficacy of one or more lens types and/or fixation sites. Seven articles had data about more than one lens type. Six had a statistical method rating of C or higher and were used to evaluate differences in visual outcomes and complication rates between lens types and fixation sites. CONCLUSIONS: The literature supports the safe and effective use of open-loop anterior chamber, scleral-sutured posterior chamber, and iris-sutured posterior chamber IOLs for the correction of aphakia in eyes without adequate capsular support for placement of a posterior chamber lens in the capsular bag or ciliary sulcus. At this time, there is insufficient evidence to demonstrate the superiority of one lens type or fixation site. Precise determination of small differences in visual outcome or complication rates will require a large prospective, randomized clinical trial.

A computerized method of visual acuity testing: adaptation of the early treatment of diabetic retinopathy study testing protocol.

PURPOSE: To develop a computerized method of visual acuity testing for clinical research as an alternative to the standard Early Treatment for Diabetic Retinopathy Study (ETDRS) testing protocol, and to evaluate its test-retest reliability and concordance with standard ETDRS testing. DESIGN: Test-retest reliability study. METHODS: Multicenter setting of a study population of 265 patients at three clinical sites. Visual acuity was measured with both the electronic visual acuity testing algorithm (E-ETDRS) and standard ETDRS protocol (S-ETDRS) twice on one eye of each patient. E-ETDRS testing was conducted using the electronic visual acuity tester (EVA), which utilizes a programmed Palm (Palm, Inc, Santa Clara, California, USA) hand-held device communicating with a personal computer and 17-inch monitor at a test distance of 3 meters. RESULTS: For the E-ETDRS protocol, test-retest reliability was high (r = 0.99; with 89% and 98% of retests within 0.1 logMAR and 0.2 logMAR of initial tests, respectively) and comparable with that of S-ETDRS testing (r = 0.99; with 87% and 98% of retests within 0.1 logMAR and 0.2 logMAR of initial test, respectively). The E-ETDRS and S-ETDRS scores were highly correlated (r = 0.96 for initial tests and r = 0.97 for repeat tests). Based on estimates of 95% confidence intervals, a change in visual acuity of 0.2 logMAR (10 letters) from a baseline level is unlikely to be related to measurement variability using either the E-ETDRS or the S-ETDRS visual acuity testing protocol. CONCLUSIONS: The E-ETDRS protocol has high test-retest reliability and good concordance with S-ETDRS testing. The computerized method has advantages over the S-ETDRS testing in electronically capturing the data for each tested letter, requiring only a single distance for testing from 20/12 to 20/800, potentially reducing testing time, and potentially decreasing technician-related bias.

Automated perimetry: a report by the American Academy of Ophthalmology.

OBJECTIVE: The purpose of this document is to summarize and evaluate the effectiveness of new automated perimetry tests and algorithms in diagnosing glaucoma and detecting disease progression. METHODS: A literature search on automated perimetry retrieved over 300 citations from 1994 to 2001, of which 71 were selected as relevant to this assessment. The quality of the evidence obtained from these studies was assessed by the methodologist. RESULTS: The four automated perimetry techniques described in this assessment are short wavelength automated perimetry (SWAP), frequency doubling technology perimetry (FDT), high-pass resolution perimetry (HPRP), and motion automated perimetry (MAP). The algorithms described are Swedish interactive threshold algorithm (SITA) and SITA fast. With the exception of SWAP, these techniques and algorithms reduce testing time and inconsistent patient performance when compared with conventional full threshold testing. CONCLUSIONS: Short wavelength automated perimetry detected visual field loss earlier than standard threshold automated perimetry, with a sensitivity and specificity of about 88% and 92% respectively. However, it is a lengthy, demanding test, is sensitive to media opacities, and has a greater magnitude of long-term fluctuation compared with standard threshold automated perimetry, which make it difficult to assess disease progression accurately. When compared to standard threshold automated perimetry, FDT perimetry showed sensitivity and specificity greater than 97% for detecting moderate and advanced glaucoma, and sensitivity of 85% and specificity of 90% for early glaucoma. As FDT perimetry has a short testing time and is resistant to blur and pupil size, it may be a useful screening tool. In a longitudinal study, high-pass resolution perimetry was more effective than standard threshold automated perimetry in monitoring progressive glaucomatous loss, detecting progression at a median of 12 months earlier in 54% of patients studied. Motion automated perimetry demonstrated usefulness in detecting early glaucomatous visual loss in a longitudinal study. Studies on SITA demonstrated greater sensitivity and reproducibility and less intertest variability when compared to standard full threshold testing and a 50% reduction in testing times. A study comparing standard full threshold, SITA, and SITA fast found a sensitivity of 95% for the first two techniques and 93% for SITA fast. Long-term follow-up studies are needed to assess the ability of these techniques to detect progression of glaucoma over time.

Decreased visual acuity associated with cystoid macular edema in neovascular age-related macular degeneration.

OBJECTIVE: To determine the prevalence and visual significance of cystoid macular edema (CME) in eyes with subfoveal neovascular age-related macular degeneration using optical coherence tomography (OCT). MATERIALS AND METHODS: The medical records of 61 consecutive patients initially seen with nondisciform subfoveal neovascular age-related macular degeneration were retrospectively reviewed. All patients underwent fluorescein angiography and OCT imaging. Eyes with intraretinal hyporeflective spaces in the macula in the OCT images were considered to have CME. RESULTS: Twenty-eight (46%) of 61 eyes demonstrated CME on the OCT images. The presence of CME and increased foveal thickness correlated with decreased visual acuity, but not with the duration of symptoms. Twenty-six (93%) of 28 eyes with CME contained classic choroidal neovascularization, whereas 16 (48%) of 33 eyes without CME contained classic choroidal neovascularization. CONCLUSIONS: Cystoid macular edema is a common finding in patients with choroidal neovascularization associated with age-related macular degeneration. The presence of CME and foveal thickening is associated with worse visual acuity in these patients. Cystoid macular edema is more common with choroidal neovascularization containing classic component. The OCT is a useful test to detect the presence of CME in these patients since CME may be difficult to identify on fluorescein angiogram.

Diagnostic yield of vitrectomy in eyes with suspected posterior segment infection or malignancy.

PURPOSE: To determine the yield of diagnostic pars plana vitrectomy in eyes with suspected posterior segment inflammation or malignancy when clinical examination and systemic laboratory testing did not yield a specific diagnosis. DESIGN: Non-comparative interventional case series PARTICIPANTS: Eighty-seven consecutive patients (90 eyes) who underwent diagnostic pars plana vitrectomy from 1989 through 1999. INTERVENTIONS: Vitreous samples were analyzed in a directed manner based on the preoperative clinical examination and systemic laboratory testing. MAIN OUTCOME MEASURES: Diagnosis from each test performed on the vitreous samples. RESULTS: Diagnostic vitrectomy was performed alone in 6 eyes (7%) and as part of a therapeutic procedure in the remaining 84 eyes. The diagnostic tests performed most frequently included cytopathology (83%), microbiologic culture and sensitivity (43%), polymerase chain reaction (PCR) (36%), and intraocular antibody levels for T. canis (14%). Of these, intraocular antibody testing and PCR had the highest positive yield, 46% and 39%, respectively. Overall, directed vitreous analysis identified a specific cause in 35 eyes (39%). Of the 65 cases in which an underlying infection was suspected preoperatively, the procedure yielded a specific diagnosis in 27 (42%). When intraocular malignancy was considered preoperatively (71 eyes), a diagnosis of intraocular lymphoma was obtained in seven (10%). This difference between these diagnostic yields was significant (P = 0.02, Fisher's exact test). CONCLUSIONS: Diagnostic vitrectomy with directed vitreous fluid analysis yields a specific cause and guides subsequent therapy in a high percentage of cases. This procedure is a valuable adjunct in cases that cannot be diagnosed by less invasive methods.

Age-related changes in vitreous mobility as measured by video B scan ultrasound.

Many vitreoretinal disorders increase in incidence with age. The vitreous is known to liquefy and separate from the retina in aging patients. Liquefaction and partial vitreous separation alter the biomechanics of the vitreous and change the tractional forces exerted by the vitreous on the retina. These forces may play a role in the development of a variety of vitreoretinal pathologies including retinal tears, cystoid macular edema, and macular holes. The purpose of this study is to test the hypothesis that the biomechanical properties of the vitreous change with aging and can be quantified by analysis of kinetic B scan ultrasound recordings. Kinetic B scan ultrasound recordings were made of the vitreous gel of 38 subjects from ages 18 to 91 during standard eye motions. The recordings were graded for speckle density (hyperreflective areas on ultrasound) and were examined for the presence or absence of posterior vitreous detachment. Tracking of the speckles on a polar grid allowed for the calculation of the angle travelled by the speckle relative to the angle travelled by the eye. The recordings were also analysed for "overshoot time", or the amount of time that the speckles continued to travel after the cessation of eye movement. The vitreous of subjects of age less than 46 years demonstrated significantly less speckle density (P < 0.001), less overshoot time (P < 0.001), and less angle travelled by the speckle relative to the angle travelled by the eye when compared to older subjects (P = 0.006). The presence or absence of PVD as diagnosed by kinetic ultrasound was not a significant predictor for speckle density, overshoot time, or ratio of angular motions. The results indicate that aging affects the biomechanics of the vitreous in ways which can be quantified with kinetic ultrasound analysis using the grading system described above.