Eytan Z. Blumenthal

Retinal nerve fibre layer imaging compared with histological measurements in a human eye.

PurposeA feasibility study comparing retinal nerve fibre layer (RNFL) thickness values obtained with imaging devices against RNFL thickness measurements obtained histologically in a human eye.DesignA single patient scheduled for orbital exenteration, who still possessed a healthy functioning eye.MethodsBefore surgery, the eye was imaged using optical coherence tomography (OCT) and scanning laser polarimetry (SLP). After orbital exenteration, the globe was sectioned, and 100 equidistant RNFL thickness measurements were obtained for each of four concentric rings centred on the optic disc, with diameters of 3.0, 3.5, 4.0, and 4.5u2009mm.ResultsRNFL thickness was found to be inversely related to the distance from the centre of the optic disc along each radial meridian. Peripapillary RNFL thickness was found comparable for histology, OCT, and SLP. RNFL thickness measured histologically confirmed a ‘double hump’ pattern, peaking at the superior and inferior poles. Histologically derived RNFL thickness (μm), at 3.0 and 3.5u2009mm diameter ring ranged between 30–135 and 25–115 respectively. In comparison, the 3.0u2009mm diameter GDx data ranged between 25 and 100, and the 3.4u2009mm diameter OCT data between 40 and 175.ConclusionsImaging data appear qualitatively similar when compared to the histologically derived data. Quantitative differences may be partly due to scaling differences and histological artefacts. The histological analysis approach demonstrated in this study can potentially serve to validate imaging-derived data, as well as help improve our understanding of RNFL loss in glaucoma.

The Learning Effect in Visual Field Testing of Healthy Subjects Using Frequency Doubling Technology

PurposeTo evaluate the presence, duration and magnitude of a learning effect in serial visual field (VF) testing, using the commercially available frequency doubling technology (FDT) instrument. Patients and Methods21 healthy adults with no prior VF experience underwent 6 serial VF tests, using the full-threshold C-20 program of the Zeiss-Humphrey FDT analyzer, on one randomly chosen eye. Tests were spaced at least two days apart. ResultsThe average mean sensitivity was 32.37 ± 2.6 dB; the average mean deviation (MD) was 1.22 ± 1.8 dB. The MD at the first examination (0.28 ± 2.1 dB) was significantly poorer than at any of the other testing sessions (p<0.003). Similarly, the mean sensitivity at the first examination (31.16 ± 3.0 dB) was significantly lower than any other testing session (p<0.004). The proportion of improvement from the first to the second session was 63% and 65% of the total improvement, for mean sensitivity and MD, respectively. Mean test duration showed a modest reduction, from 4.40 ± 0.3 minutes in the first session to 4.17 ± 0.4 minutes in the last session (p = 0.023). A sub-analysis comparison of the different VF segments showed a more prominent learning effect in the peripheral and nasal visual segments (p<0.0001). ConclusionBaseline measurements should best rely on the second testing session, since MD and mean sensitivity are somewhat poorer when subjects with no prior VF experience are first tested on the FDT instrument. This may be especially true for the purpose of following patients over time.

Morphometric Analysis of Human Peripapillary Retinal Nerve Fiber Layer Thickness

PURPOSEnThe peripapillary retinal nerve fiber layer (RNFL) thickness pattern in the normal human eye has been well characterized using data obtained with scanning laser polarimetry and optical coherence tomography. The authors sought to characterize the normative peripapillary RNFL thickness and pattern using histologic sections obtained from healthy postmortem human eyes.nnnMETHODSnSeventeen unpaired normal postmortem eyes were recruited into this study. Each eye was sectioned using the umbrella technique to obtain four concentric peripapillary rings, each centered on the optic disc, with diameters of 3.0, 3.5, 4.0, and 4.5 mm. RNFL thickness data along each ring section was measured at 100 equidistant locations. Thickness data, for each ring diameter, across all eyes were averaged to arrive at normative thickness values for the peripapillary RNFL thickness in eyes processed using this technique.nnnRESULTSnAverage RNFL thicknesses (+/-SD) for the 3.5-mm diameter ring were as follows: overall, 60.3 +/- 19.5 microm; superior, 75.3 +/- 26.5 mum; inferior, 69.4 +/- 22.4 microm; nasal, 48.1 +/- 15 microm; temporal, 49.2 +/- 26.4 microm. Qualitatively, the RNFL thickness showed a double-hump pattern with relatively similar superior and inferior peaks and with temporal and nasal troughs. Progressively larger peripapillary rings showed progressively thinner RNFL thickness at all quadrants. In contrast, the relative thickness percentage for each quadrant remained unchanged among the four different diameter rings.nnnCONCLUSIONSnHistologic data from a group of healthy postmortem eyes demonstrate the pattern of RNFL thickness in normal eyes. These data corroborate imaging findings of peripapillary RNFL thickness patterns obtained using commercially available RNFL imaging devices.

Misleading statistical calculations in far-advanced glaucomatous visual field loss.

OBJECTIVEnIn this study, the capability of statistical analysis indices to characterize static automated visual fields (VFs) accurately in cases of far-advanced glaucoma was assessed.nnnDESIGNnRetrospective observational case series.nnnPARTICIPANTSnSixteen eyes of 15 patients with end-stage glaucoma and evidence of collapse of VF statistical analysis indices were included in the study.nnnMETHODSnEnd-stage glaucoma was defined as vertical cup-to-disc ratio of 0.9 or more, mean deviation less than -24 dB and with only a central or temporal island remaining in the VF gray scale. Collapse of statistical indices was defined as any of the following: pattern deviation probability plot without a single VF location showing P < 0.5%; corrected pattern standard deviation (CPSD) and pattern standard deviation (PSD) probability less than 5% or within normal limits (WNL); short-term fluctuation (SF) probability WNL; glaucoma hemifield test (GHT) not outside normal limits (ONL); or presence of a low patient reliability comment triggered by 40% or more false-negative (FN) responses.nnnMAIN OUTCOME MEASURESnVisual field statistical indices.nnnRESULTSnOf the 16 VFs showing misleading statistical calculations, 9 of 16 eyes had a normal pattern deviation probability plot. The PSD, SF, and CPSD parameters were normal or barely outside the normal range in 4 of 16, 10 of 16, and 5 of 16 eyes, respectively. The GHT was ONL in 7 of 13 eyes, borderline with generalized reduction of sensitivity (GRS) in three eyes, and only GRS in two additional eyes. Low patient reliability was triggered because of an FN score of 40% or more in 10 of 16 eyes.nnnCONCLUSIONSnStatistical indices are crucial for the interpretation of automated static VFs. However, in end-stage glaucomatous VF loss, both summary statistical indices and reliability indices may not detect abnormality, thus misleading the casual observer.

Correlating structure with function in end-stage glaucoma.

To determine whether prone postoperative near visual acuity following macular hole surgery can be used as a reliable indicator of successful hole closure, data from 21 patients undergoing macular hole surgery were collected. Seventeen of the 18 patients with hole closure and all 3 patients with persistent macular holes had a Rosenbaum acuity better than preoperative visual acuity, yielding 94% sensitivity, 0% specificity, 85% positive predictive value, and 0% negative predictive value. Fourteen of the 18 patients with macular hole closure and all 3 patients with persistent macular holes had a Rosenbaum acuity better than 20/40, yielding 78% sensitivity, 0% specificity, 82% positive predictive value, and 0% negative predictive value. Although postoperative near visual acuity can predict macular hole closure with 94% sensitivity, the test is not clinically useful to predict hole closure because of the high surgical success rate of macular hole surgery. The test could be useful in encouraging patients to maintain head prone positioning and alleviate patient anxiety.

The role of preoperative ultrasonography for patients with dense cataract: a retrospective study of 509 cases.

BACKGROUND AND OBJECTIVEnOcular ultrasonography is widely used for the evaluation of eyes with opaque ocular media. Although preoperative ultrasonography of the globe has been recommended for patients with dense cataracts, the value of such an examination is currently unknown. The purpose of this study was to evaluate the prevalence and nature of intraocular pathologies detected by preoperative ultrasound examination in patients with dense cataract.nnnPATIENTS AND METHODSnThe authors retrospectively studied 509 patients referred for routine ultrasound examination of the globe due to dense cataract. Exclusion criteria included known posterior segment pathology, previous ocular surgery or penetrating trauma, and age of younger than 18 years. All the patients underwent ultrasound examination by B-scan and standardized A-scan.nnnRESULTSnIn 19.6% of the patients, a posterior segment pathology was revealed by the ultrasound examination. The most frequently disclosed abnormalities were posterior staphyloma (7.2%), retinal detachment (4.5%), and vitreous hemorrhage (2.5%). One patient with a large choroidal malignant melanoma was identified. The prevalence of posterior segment pathologies was slightly higher in patients with a history of ocular trauma, compared with the nontraumatic cataract group (29.6% versus 19.0%, respectively; P = .1). The prevalence of retinal detachment was increased in the traumatic cataract subgroup (14.8% compared with 3.9%), but this difference did not reach statistical significance.nnnCONCLUSIONnPreoperative ultrasound examination for patients with dense cataract can be used to detect pathologies that may influence the surgical strategy and the postoperative visual prognosis.

Measurement of Choroidal Melanoma Basal Diameter by Wide-Angle Digital Fundus Camera: A Comparison with Ultrasound Measurement

Purpose: To compare the measurement of the basal diameter of choroidal melanoma, an important parameter for planning treatment and as a prognostic factor, by standardized ophthalmic ultrasound versus that obtained using a wide-angle fundus camera. Methods: The longest and shortest basal diameters of 104 consecutive choroidal melanomas of patients seen at the ocular oncology service of the Hadassah University Hospital were measured by B-scan ultrasound and compared with those measured by a wide-angle fundus camera (Panoret-1000). Each diameter was measured thrice by two ophthalmic photographers, and intra-observer and interobserver reproducibility were calculated as well. Results: The measurements of both the long and short diameters of the choroidal melanomas were significantly larger when measured by Panoret-1000 as compared with the B-scan ultrasound. There was no significant difference among the three measurements of each of the photographers. The interobserver reproducibility between the two photographers was high. Conclusions: Our findings can be attributed to the larger extent of the pigmentation of the melanoma compared to its recognized elevation. Since pigmentation of choroidal melanoma is easier to recognize than its elevation, we assume that measurement by a wide-angle fundus camera is more accurate in pigmented tumors, and should be adopted for measuring the basal diameter of choroidal melanomas in planning treatment and follow-up.

Trabeculectomy and phaco-trabeculectomy with and without peripheral iridectomy

Purpose To compare the 1-year outcome of trabeculectomy and combined phaco-trabeculectomy that were performed with or without a peripheral iridectomy (PI). Methods In a large tertiary glaucoma clinic, with a single surgeon performing all surgeries, 47 patients scheduled to undergo either a primary trabeculectomy or phaco-trabeculectomy were prospectively randomized to surgery with or without peripheral iridectomy. Other than the inclusion (PI group) or omission (no PI group) of a PI, surgical technique and postoperative care were identical for the two groups. The two groups were compared for intraocular pressure (IOP), success rates, visual acuity (VA), and complication rates. Complete and qualified success rates were defined as IOP 18 mmHg or less with or without medications, respectively. Results The 1-year complete and qualified success rates were comparable for both groups. Complete success was observed in 70% of cases, and qualified success in more than 90%. One patient (4.3%) from the no-PI group developed an iris incarceration into the internal sclerectomy site on postoperative day 1, requiring surgical intervention. No other significant complications (blebitis, endophthalmitis, or choroidal hemorrhage) were encountered in any of the study patients. Conclusions This randomized prospective small scale study explored the possibility of sparing the need to perform a routine PI in trabeculectomy and phaco-trabeculectomy. These preliminary results suggest that the outcomes in the two groups are comparable, paving the way to a larger scale study evaluating the need for PI in modern trabeculectomy surgery.

Could cancer be a physiological phenomenon rather than a pathological misfortune

The hypothesis presented here is that cancer is not a phenomenon where the normal functions of the human body break down (like diabetes mellitus or renal failure) but rather a well planned and well coordinated physiological response (similar to the inflammatory response). Cancer initiating genes are presumed neoplastic DNA sequences involved in sensing genome deterioration, consequently enhancing preservation. This genetic trait, different from the concept of oncogenes, actively triggers the neoplastic transformation once genome deterioration is sensed. This self destructive, altruistic phenomenon, obviously devastating to the organism, is nevertheless shown to be a possible mechanism of natural selection. The survival advantage of cancer initiation is discussed using both the concepts of group selection and gene selection. Natural selection, the driving force of evolution, is believed to operate solely on the basis of phenotype differences among individuals. In this paper cancer is hypothesized to be a mechanism that directly scrutinizes the gene contents of the individual, therefore representing natural selection based on genotype differences.

Glaucomatous-Like Cupping Associated with Slow-Growing Supra-Sellar Intracranial Lesions

Purpose: To demonstrate that slow-growing intracranial suprasellar mass lesions can be associated with optic disc cupping, clinically indistinguishable from glaucomatous optic neuropathy. Cases: At a neuro-ophthalmology tertiary clinic, a retrospective chart review identified four patients of presumed normal tension glaucoma and supra-sellar tumors. In all four patients with normal intraocular pressure, the appearance of the optic disc resembled typical glaucomatous optic nerve damage with disc cupping and parapapillary atrophy. Conclusion: In few patients, typical glaucomatous abnormalities of the optic nerve head may occur in association with slow-growing suprasellar tumors.