Nathaniel E. Knox Cartwright

3D Collagen Orientation Study of the Human Cornea Using X-ray Diffraction and Femtosecond Laser Technology

PURPOSE To study the distribution and predominant orientations of fibrillar collagen at different depths throughout the entire thickness of the human cornea. This information will form the basis of a full three-dimensional reconstruction of the preferred orientations of corneal lamellae. METHODS Femtosecond laser technology was used to delaminate the central zones of five human corneas into three separate layers (anterior, mid, and posterior stroma), each with predetermined thicknesses. Wide-angle x-ray diffraction was used to study the gross collagen fibril orientation and distribution within each layer. RESULTS The middle and posterior parts of the human cornea demonstrated a preferential orthogonal arrangement of collagen fibrils, directed along the superior-inferior and nasal-temporal meridians, with an increase in the number of lamellae toward the periphery. However, the anterior cornea (33% of total corneal thickness) showed no systematic preferred lamellar orientation. CONCLUSIONS In the posterior two thirds of the human cornea, collagen lies predominantly in the vertical and horizontal meridians (directed toward the four major rectus muscles), whereas collagen in the anterior third of the cornea is more isotropic. The predominantly orthogonal arrangement of collagen in the mid and posterior stroma may help to distribute strain in the cornea by allowing it to withstand the pull of the extraocular muscles, whereas the more isotropic arrangement in the anterior cornea may play an important role in the biomechanics of the cornea by resisting intraocular pressure while at the same time maintaining corneal curvature.

First Eye Prediction Error Improves Second Eye Refractive Outcome Results in 2129 Patients after Bilateral Sequential Cataract Surgery

OBJECTIVE To define theoretical correction factors for second-eye intraocular lens (IOL) power adjustment based on first eye refractive prediction error (PE). DESIGN Database study. PARTICIPANTS We included 2129 patients who underwent bilateral sequential phacoemulsification cataract surgery with the same IOL model. METHODS Retrospectively calculated PEs (Hoffer Q, Holladay 1, SRK/T) were analyzed for association between paired eyes, examining the effect of interocular differences in axial length (AL) and corneal power. A range of correction factors (CF) derived from the first eye PE were applied to the second eye PE using optimized and non-optimized IOL constants (IOLCs). MAIN OUTCOME MEASURES Second eye mean absolute error (MAE). RESULTS Prediction errors of paired eyes were correlated. Interocular corneal power differences exceeding 0.60 diopters (D) were associated with a weaker correlation but interocular AL differences did not affect the correlation. When a 50% CF was applied to second eyes of patients with a first eye PE between ±0.50 and ±1.50 D, it improved refractive outcomes from 30%, 56%, and 92% to 42%, 75%, and 96% within ±0.25 D, ±0.50 D and ±1.00 D, respectively, and reduced the MAE from 0.49 to 0.37 D (P<0.0001). For first eye PE below ±0.50 D, a 50% CF reduced the MAE from 0.32 to 0.30 D (P<0.00001). A 50% CF also reduces second eye MAE for eyes with nonoptimized IOLCs. CONCLUSIONS A 50% CF reduces second eye PE when either first eye optimized PE is within ±1.50 D or when nonoptimized IOLCs are used. The correlation is weaker when interocular corneal power differences are >0.60 D.

Adjustment of intraocular lens power for sulcus implantation

The SRK/T formula was developed with reference to data from 1677 eyes; T2 was developed using data from 5588 eyes. The original analysis of the performance of the SRK/T formula evaluated 1050 eyes, and the 3 largest independent series analyzed between 786 and 858 eyes. Our analysis of the relative performance of the SRK/T and T2 formulas examined 5601 eyes. This is the largest such series published to date and by somemargin. The discovery of the SRK/T cusp was attributed to Ken Hoffer and Alan Ritter and first reported in 1992. In 1993, the authors of the SRK/T formula acknowledged that the cusp was “an unexpected side effect” and stated that they were “gathering data.to determine the best method of adjusting the SRK/T formula to eliminate the cusp and, if possible, to improve IOL power prediction.” In the intervening 17 years, nothing further has been published. We have simply applied the scientific method and have succeeded on both counts. The SRK/T formula authors believed that the cusp phenomenon affected only a small percentage of eyes with high corneal powers. We demonstrated that this is not the case; the SRK/T formula contains a systematic error that affects eyes with high and low corneal powers to the greatest degree, but the error in corneal height prediction has some effect for any eye that is not close to average axial length and corneal power.

Uncited biometry study

Uncited biometry study In Hoffman and H€ utz’s recent paper describing the ocular biometric characteristics of 15 448 patients attending their clinic in Germany and the related editorial, the authors state that they believe this analysis to be the largest ocular biometric study to date and the first in the era of partial coherence interferometric axial length (AL) measurement. In fact, more than a year ago, our group, also using the IOLMaster with software version 3.0 (Carl Zeiss Meditec AG), reported the ocular biometric characteristics of 32 556 eyes, 14 016 of which were paired. The mean AL was 23.40 mm G 1.32 (SD) and the mean Kmean, 43.90 G 1.55 diopters (equivalent to a mean radius of anterior corneal curvature of 7.69 mm if a keratometric index of 1.3375 is assumed), values almost identical to those described by Hoffman and H€ utz. Surprisingly, we did not find a change in Jaeger (J)45 or J0 power vectors with age. Unlike in the Hoffman and H€ utz’s study, the corneal diameter, phakic anterior chamber depth, and emmetropic intraocular power were not determined. Although the similarity of results obtained in these 2 studies validates the methodology used in each, it is uncertain whether these findings can be extrapolated to non-European populations.

Lack of Statistical Power and Refractive Outcomes

In their excellent study, Sahin et al. investigated the effect of diabetes mellitus on various corneal biomechanical parameters, as measured by the Ocular Response Analyzer (ORA; Reichert, Inc., Depew, NY). The rationale of their study is very interesting. To my surprise, the authors showed a decrease in corneal hysteresis (CH) rather than the expected increase. Several factors suggest that diabetes mellitus would actually enhance corneal biomechanics by an increase in the crosslinking rate: First, an earlier retrospective study showed a lower incidence of keratoconus in diabetic patients, suggesting that corneal biomechanics are enhanced in diabetic corneas. Second, the nonenzymatic glycosylation of proteins (Maillard reaction) that is prominent in diabetes mellitus, results in the formation of advanced glycosylation end products (AGEs). AGEs induce cross-links between connective tissue collagen and increase tissue rigidity, especially in the presence of glucose. Similar to diabetes, tobacco smoking represents a source of AGEs, and moreover, by-products of cigarette smoke, such as nitrogen oxides, nitrite, and formaldehyde, induce cross-links between collagen fibers. A recent epidemiologic study showed that the incidence of keratoconus in smokers is considerably lower than in the nonsmoking population, and we have recently performed a prospective comparative case series to investigate the effect of chronic tobacco smoking on corneal biomechanics using the ORA. Our results showed that chronic smoking increases corneal rigidity in a statistically significant manner. The study by Sahin et al. shows the opposite and was performed in Turkey. From 1990 to 1999, Turkey had the second highest growth rate in cigarette consumption in the world, and in 1999, Turkey accounted for 2.2% of the total world cigarette consumption. Therefore, accounting for the smoking status of the participants in this study would be essential for the outcome and might have significantly altered the results. The authors could not be aware of the influence chronic tobacco smoking might have on their results, because at the time of publication of their study our paper, now published, was in press. I therefore suggest that Sahin et al. determine the smoking status of their patients and perform the statistical analysis in light of their findings. Farhad Hafezi