Yair Morad

Corneal thickness and curvature in normal-tension glaucoma

PURPOSE To determine whether normal-tension glaucoma, defined as a condition in which glaucomatous optic nerve and visual field changes exist without documentation of intraocular pressure greater than 21 mm Hg or other apparent cause for these changes, is overdiagnosed in patients with decreased central corneal thickness and curvature. METHODS Twenty-one patients with normal-tension glaucoma were compared with 25 patients with primary open-angle glaucoma and 27 age-matched healthy subjects. Corneal thickness was determined by ultrasonic pachymetry. Corneal curvature was determined using a keratometer. Eyes with corneal pathology or previous intraocular surgery were excluded. RESULTS Mean corneal thickness +/- SD in 21 eyes of 21 patients with normal-tension glaucoma was 0.521 +/- 0.037 mm, significantly (P = .0028) lower than in 25 eyes of 25 patients with primary open-angle glaucoma (0.556 +/- 0.035 mm) and 27 eyes of 27 healthy subjects (0.555 +/- 0.034). Mean corneal curvature in the three groups was not appreciably different: 43.90 +/- 1.81 diopters, 43.66 +/- 1.68 diopters, and 44.36 +/- 1.13 diopters in the patients with normal-tension glaucoma and primary open-angle glaucoma and the healthy subjects, respectively. CONCLUSIONS Corneal thickness is significantly reduced in patients with normal-tension glaucoma compared with patients with primary open-angle glaucoma (P = .0028) and normal subjects (P = .0037). This may lead to underestimation of intraocular pressure and misdiagnosis in some of these patients. Corneal curvature was similar in patients with normal-tension glaucoma and primary open-angle glaucoma and in healthy subjects.

Clinical and corneal biomechanical changes after collagen cross-linking with riboflavin and UV irradiation in patients with progressive keratoconus: results after 2 years of follow-up.

Purpose: To assess the biomechanical and keratometric effects and the safety of treatment of progressive keratoconus with UV–riboflavin collagen cross-linking (CXL). Methods: This is a prospective clinical controlled study. Fourteen eyes of 14 patients with progressive keratoconus were treated with CXL after corneal deepithelization. Patients were assessed preoperatively, at week 1 and at months 1, 3, 6, 9, 12, and 24 after treatment. We measured uncorrected visual acuity (UCVA) and best spectacle–corrected visual acuity (BSCVA) (logarithm of the minimum angle of resolution), refraction, biomicroscopy and fundus examination, intraocular pressure, axial length, endothelial cell density, corneal topography, minimal corneal thickness, macular optical coherence tomography, and corneal biomechanics with the ocular response analyzer. Results: Comparing the preoperative results with 24-month postoperative results, we observed significant improvement in BCVA (0.21 ± 0.1 to 0.14 ± 0.1, P = 0.002) and stability in UCVA (0.62 ± 0.5 and 0.81 ± 0.49, P = 0.475). We observed a significant decrease in steepest-meridian keratometry (diopters) (53.9 ± 5.9 to 51.5 ± 5.4, P = 0.001) and in mean cylinder (diopters) (10.2 ± 4.1 to 8.1 ± 3.4, P = 0.001). Significant elongation of the eyes was observed, from 24.39 ± 1.7 mm to 24.71 ± 1.9 mm (P = 0.007). No significant change was observed in mean simulated keratometry, minimal corneal thickness, endothelial cell density, corneal hysteresis, and corneal resistance factor or foveal thickness. Conclusions: Two years after CXL, the observation of stable UCVA, improved BCVA, and reduced keratometry suggests stabilization in progression of keratoconus. Unchanged corneal thickness, endothelial cell density, and foveal thickness suggest the long-term safety of this procedure. The observed increase in axial length and stability in corneal biomechanical parameters measured with the ocular response analyzer require further study for verification and explanation.

Angiogenesis in pterygium: Morphometric and immunohistochemical study

Objective. To evaluate the role of angiogenesis in the pathogenesis of pterygium by comparing the expression of von-Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) in pterygium, and in normal superior bulbar conjunctiva. Methods. 23 human samples from pterygium and the superior bulbar conjunctiva were stained using rabbit anti-vWF and anti-VEGF antibodies. The density of vWF and VEGF positive vessels, VEGF staining intensity and the number of VEGF positive stromal, epithelial and vascular endothelial cells were evaluated. Results. Pterygium specimens had higher average vWF and VEGF positive microvascular counts per high power field (P = 0.0012), higher average VEGF staining intensity scores in epithelial, stromal and endothelial cells (p < 0.0001) and higher VEGF positive cell counts (P < 0.0001) than normal conjuctiva. Conclusions. Over-expression of VEGF in pterygium tissue, together with the abundance of vWF-stained new vessels, may support previous suggestions that angiogenesis may play a role in the formation of pterygium.

Effect of diabetes mellitus on biomechanical parameters of the cornea.

PURPOSE: To compare parameters of biomechanical response of the human cornea measured as corneal hysteresis (CH) and corneal resistance factor (CRF) in patients with diabetes mellitus and healthy control subjects. SETTING: Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, Israel. METHODS: In the right eye of each participant, the CH, CRF, Goldmann‐correlated intraocular pressure (IOPg), and corneal‐compensated intraocular pressure (IOPcc) were measured with the Ocular Response Analyzer. Central corneal thickness (CCT) was measured by ultrasonic pachymetry and intraocular pressure by Goldmann applanation tonometry (IOP GAT). Findings were compared between the 2 groups (control and diabetic). RESULTS: Forty diabetic patients (17 women, 23 men) and 40 healthy subjects (19 women, 21 men) were prospectively recruited. The mean CH was 9.3 mm Hg ± 1.4 (SD) and 10.7 ± 1.6 mm Hg and the mean CRF was 9.6 ± 1.6 mm Hg and 10.9 ± 1.7 mm Hg in the control group and diabetic group, respectively (both P < .0001). Diabetic corneas were significantly thicker (P = .019); the mean CCT was 530.3 ± 35.9 μm in the control group and 548.7 ± 33.0 μm in the diabetic group. The CH and CRF remained significantly different in multivariate analysis that included CCT. There was no statistically significant difference between the 2 groups in IOPcc, IOPg, or IOP GAT measurements. CONCLUSIONS: Diabetes mellitus affected biomechanical parameters of the human corneas, including increased CH, CRF, and CCT. Whether this observation has implications in the clinical management and understanding of corneal ectasia and glaucoma requires further study.

Can we measure corneal biomechanical changes after collagen cross-linking in eyes with keratoconus?--a pilot study.

Purpose: To assess changes in biomechanical properties of human cornea after treatment of keratoconus with UV-A-riboflavin corneal collagen cross-linking (CXL). Design: Single-center, prospective, interventional study. Methods: Ten eyes of 10 patients aged 26.5 ± 5.7 (mean ± SD) years with progressive keratoconus were treated with UV-A-riboflavin CXL and assessed with the Ocular Response Analyzer (ORA) that measured corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal compensated intraocular pressure (IOPcc). Intraocular pressure was also measured by Goldmann applanation tonometry (GAT-IOP). Patients were assessed with ORA preoperatively, at week 1, months 1, 3, and 6 after treatment. Postoperative measurements at each visit were compared with preoperative values. Results: CH and CRF were transiently elevated after cross-linking treatment, with the difference not statistically significant (P > 0.3). IOPcc and IOPg were statistically significantly higher at 1 week and 1 month but not subsequently (P < 0.04). GAT-IOP was statistically significantly higher at 1 week and at 1 and 3 months (P < 0.01). Conclusions: There were no significant differences in corneal biomechanical properties, as measured with the ORA parameters CH and CRF, after CXL in keratoconus. IOPcc, IOPg, and GAT-IOP values were transiently elevated after CXL treatment in our study. Whether this reflects a measurement artifact resulting from corneal changes or true elevation of intraocular pressure is unclear.

Topical Tacrolimus 0.03% Ointment for Intractable Allergic Conjunctivitis: An Open-Label Pilot Study

Purpose: To evaluate the feasibility of tacrolimus 0.03% dermatological ointment (Protopic) in the treatment of intractable allergic conjunctivitis. Methods: Twenty patients (mean age 10.8 years, range 6–26) with intractable allergic conjunctivitis were enrolled in an open-label study. Tacrolimus 0.03% ointment was applied into the conjunctival sac of both eyes twice daily for 8 weeks, followed by a 2-week washout period. Other ocular medications were discontinued. Conjunctivitis severity was recorded with a composite subjective/objective score (chemosis, tarsal papillary size, corneal staining, tearing, itching, and photophobia) at baseline, week 8, and after washout. Tacrolimus blood levels were measured at 2 weeks. Results: Statistically significant improvement in all categories of the conjunctivitis score was observed between baseline and the week 8 examination (p < 0.001). Adverse events were limited to local burning in one patient who discontinued treatment. Blood tacrolimus levels were mostly undetectable. Conclusions: Application of tacrolimus 0.03% dermatological ointment into the conjunctival sac appears to be effective, well tolerated, and safe in the treatment of allergic conjunctivitis refractory to traditional treatment.

Pupillography as an objective indicator of fatigue

PURPOSE To determine whether parameters calculated from pupillary activity can identify subjects with sleep deprivation, and whether the objective values correlate with a subjective feeling of fatigue. METHODS pupil size in the dark was recorded continuously for 10 minutes in 12 healthy volunteers using an infrared video camera. Two recordings were made for each subject: after a full nights sleep, and after 24 hours of sleep deprivation. Several parameters calculated from pupil size and activity were analyzed and compared with a subjective rating of the state of alertness provided by the participants in each test. RESULTS All pupillary parameters differed significantly between alertness and fatigue (p = 0.0076-0. 0186). Changes in one of the parameters - average pupillary diameter - correlated with changes in the subjective level of sleepiness (r = -0.51, p = 0.028). Although the values of most parameters differed among subjects, an absolute value of more than 25 in one parameter, cumulative pupillary variability ratio, was always associated with sleep deprivation. CONCLUSION On-line analysis of the pupillogram using the suggested parameters can be performed easily to produce a real-time assessment of an individuals state of alertness or fatigue that correlates with his/her subjective assessment of this state.

Penetrating keratoplasty for keratoconus: long-term results.

Purpose: To study central corneal endothelial cell density and morphology and corneal topography in transplanted corneas for keratoconus 10 to 17 years postoperatively. Methods: Retrospective, noncomparative case series including all keratoconus patients who underwent penetrating keratoplasty by one surgeon, at the same center, between January 1986 and December 1994. Seventeen patients (22 eyes) met the criteria. Four patients (5 eyes) with unchanged visual acuity during the follow-up period did not agree to return for the last follow-up examination, 1 patient (1 eye) had graft failure, and 3 patients (4 eyes) were lost to follow-up. We reviewed the charts of 9 patients (12 eyes), and collected data including manifest refraction, best corrected visual acuity (BCVA), endothelial cell density, cell morphology, and corneal topography. Results: The mean follow-up period for all eyes evaluated was 13.3 ± 2.4 years (range 10-17 years). At the last follow-up, 91.7% of eyes achieved BCVA of 20/40 or better, and mean endothelial cell density was 695 ± 113.6 cells/mm2. Pleomorphism was detected in 5 eyes. Keratoconus pattern, by corneal topography, was not detected in any eye at the final examination. Conclusions: Endothelial cell count 10-17 years post-PKP for keratoconus is very low with pleomorphism and viable grafts, indicating continued endothelial instability.

Brief posturographic test as an indicator of fatigue

Abstract  The purpose of the present paper was to analyze the efficiency of an abbreviated, albeit objective posturographic test as an indicator of fatigue. Posturography was measured in 10 healthy adults (age 18–33 years, male/female 7/3). Baseline posturographic measurements were taken for each subject. Later, a shorter (3‐min) posturographic test was administered 12 times during 25 h of sleep deprivation. This was correlated with subjective assessment of fatigue using a questionnaire and cognitive performance assessed with a reaction time test (Psychomotor Vigilance Test). Although showing significant individual differences, the score of the abbreviated posturographic examination, normalized to each subject’s baseline performance (‘fatigue index’) had a pronounced circadian pattern with a peak of instability in the early morning hours. Fatigue index was highly correlated with the cognitive test (r = 0.80–0.90). A substantial, albeit weaker correlation was found between the fatigue index and the subjective fatigue scores (r = 0.59–0.75). Fourier spectral analysis showed that low median sway (0.10–0.50 Hz), considered to be an expression of vestibular control, was most affected by fatigue. The study demonstrates that cognitive deterioration caused by fatigue can be objectively predicted by an abbreviated postural test of ≤3 min. This test is promising to be valid, reliable, and practicable, while being significantly correlated with physiological markers and validated cognitive measures of fatigue obtained by substantially more time‐consuming and less convenient methods.

Guidelines for Postmortem Protocol for Ocular Investigation of Sudden Unexplained Infant Death and Suspected Physical Child Abuse

Postmortem examination is a cornerstone in identifying the cause of unexplained sudden death in children. Even in cases of suspected or known abuse, an autopsy may help characterize the nature of the abuse, which is particularly important in the forensic autopsy of children in the first 3 to 4 years of life when inflicted neurotrauma is most common. Forensic examinations are vital in cases that might otherwise be diagnosed as sudden infant death syndrome. The ocular autopsy in particular may demonstrate findings that were not appreciated on antemortem clinical examination. This protocol for postmortem examination of the eyes and orbits was developed to promote more consistent documentation of findings, improved clinical and forensic decision making, and more replicable and coherent research outcomes.