Mouhamed Al-Aqaba

Architecture and distribution of human corneal nerves

Aims To comprehensively study the gross anatomy of human corneal innervation. Methods Twenty-one specimens, including 12 normal human corneas from seven deceased patients, two eye-bank corneo-scleral buttons, two eye-bank corneo-scleral rims and five post-surgical specimens from three patients with keratoconus were studied. Corneal whole mounts were stained for cholinesterase enzyme using the Karnovsky & Roots direct colouring thiocholine modification of acetylcholinesterase (AchE) technique. Results Approximately 44 thick nerve bundles were found to enter the human cornea in a relatively equal distribution round the limbus and move randomly towards the central cornea. At the mid-peripheral zone, anterior stromal nerves showed a characteristic budding and branching pattern. After passing through Bowmans zone they were noted to terminate into bulb-like thickenings from which multiple sub-basal nerves arose. The perforation sites were predominantly located in the mid-peripheral cornea. The orientation of sub-basal nerves was mainly vertical at their origin from the perforation sites. Nerves from all directions converged towards the infero-central cornea to form a characteristic clockwise whorl pattern. Conclusions This study provides a comprehensive account of the architecture and distribution of nerves in the human cornea. It reconciles some of the existing information obtained from other modalities of investigation and identifies some novel features that provide a more complete picture of corneal innervation.

Corneal densitometry as an indicator of corneal health.

PURPOSE To establish prospectively the normal values of corneal density of healthy subjects using the Pentacam Scheimpflug system (Oculus, Inc., Wetzlar, Germany) and to investigate alteration in corneal density during active and healed stages of bacterial keratitis. DESIGN Prospective, comparative case series. PARTICIPANTS AND CONTROLS Sixty-four eyes of 40 healthy controls and 36 eyes of 35 patients with bacterial keratitis were studied. METHODS This study was conducted at the Queens Medical Centre, Nottingham, United Kingdom. A Pentacam system was used to study corneal density. Corneal densitometry readings in subjects with bacterial keratitis were recorded during the active stage and 4 to 6 weeks after complete healing. Densitometry was recorded at the site of infection and at a point in clear cornea furthest away from the infectious infiltrate. Corneal thickness also was measured. MAIN OUTCOME MEASURES Densitometry values of normal cornea, at the site of corneal ulcer or abscess, and at a distant point of clear cornea during active and healed keratitis. RESULTS The mean densitometry value of normal corneas was 12.3 ± 2.4. In infectious keratitis, the densitometry values were greatest at the site of the active infection and significantly more than in controls. The densitometry values at the points of clear cornea furthest away from the site of infection also were significantly higher than in controls during active disease, but failed to return to normal values, despite complete resolution of infection. The density of the infiltrates was much higher than that of residual scars after healing of ulcers. No correlation was found between the pachymetry and the densitometry values. CONCLUSIONS Densitometry of active infectious corneal infiltrates is more than that resulting from the corneal scarring after healing. Persistent increase in density of clear cornea furthest away from the focus of corneal infection suggests that the host response extends beyond the immediate area of infection and indeed may occur through the entire cornea. These changes persist beyond 4 weeks of healing, which was the duration of follow-up of this study. Densitometry can be used as an objective measure of the corneal response to infection and to monitor response to therapy.

Ex vivo confocal microscopy of human corneal nerves.

Aims To evaluate the distribution, morphometry and the postmortem changes of the central and peripheral human corneal nerves by exvivo laser-scanning confocal microscopy (EVCM). Methods 24 eyes from 14 cadavers were retrieved at different time intervals after death and examined by EVCM. Five regions were examined in each eye: central, superior, inferior, temporal and nasal. In each region, corneal nerve images were categorised according to their anatomical location in the cornea into sub-basal, stromal and limbal nerves. Five nerve parameters were measured: density, orientation, diameter, numbers and branching pattern. Results Exvivo confocal scanning of a motionless eye allows high quality imaging and tracking of corneal and limbal nerves. Stromal nerves from the sub-Bowmans plexus perforate the Bowmans zone and terminate in bulb-like structures, from each of which a leash of sub-basal nerves arises. Following death, sub-basal nerve parameters showed significant changes. The density decreased from 9.23±4.48 to 0.45±0.07 mm/mm2, the diameter from 4.01±0.81 to 2.08±0.20 μm, the numbers from 8.3 to 1.0 and branching pattern from 39.38% to 0% (p<0.05) from day 1 to day 5 postmortem. Stromal and limbal nerves showed no significant changes in their density and diameter. Conclusions This study establishes a direct link between sub-basal nerves and the sub-Bowmans nerves via distinct terminal bulbs. Limbal nerves are the thickest, are seen in all quadrants and can be traced to the corneal centre. The sub-basal nerve plexus rapidly degenerates after death but stromal and limbal nerves survive during the first five days after death.

Wavefront-optimized excimer laser in situ keratomileusis for myopia and myopic astigmatism: refractive outcomes and corneal densitometry.

PURPOSE: To determine the refractive outcomes of wavefront‐optimized laser in situ keratomileusis (LASIK) treatments, in particular to measure corneal densitometry after LASIK using the densitometry function of the Pentacam Scheimpflug system. SETTING: Division of Ophthalmology and Visual Sciences, University of Nottingham, United Kingdom. DESIGN: Cohort study. METHODS: Changes in postoperative visual acuity, refraction, and contrast sensitivity were evaluated after wavefront‐optimized laser treatment. Corneal densitometry was evaluated with the Scheimpflug system before and after LASIK. RESULTS: One year postoperatively, the uncorrected distance visual acuity was 6/6 or better in 92% of eyes and 6/9 or better in all eyes. Eighty‐six percent of eyes had no change in the corrected distance visual acuity (CDVA); 4% gained 1 or more lines. Wavefront‐optimized LASIK was stable over 1 year postoperatively. Eighty‐nine percent of eyes were within ±0.50 diopter (D) and 100% were within ±1.00 D of the intended correction 1 year postoperatively. Contrast sensitivity showed a nonsignificant improvement (1.55 ± 0.10 [SD] preoperatively to 1.57 ± 0.09 12 months postoperatively) (P > .05). There was a nonsignificant increase in corneal densitometry 1 year postoperatively (from 12.72 ± 2.43 to 13.04 ± 2.58) (P > .05). No correlation was found between corneal densitometry and contrast sensitivity or CDVA. CONCLUSIONS: Wavefront‐optimized LASIK gave excellent refractive and visual outcomes and did not seem to affect corneal densitometry significantly 1 year postoperatively. However, larger studies may show a masked effect on corneal densitometry. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

The effect of standard and transepithelial ultraviolet collagen cross-linking on human corneal nerves: an ex vivo study.

PURPOSE To evaluate the early effect of standard and transepithelial collagen cross-linking on human corneal nerves in donor eyes by ex vivo confocal microscopy and acetylcholinesterase staining. DESIGN Experimental laboratory investigation. METHODS Eight human eye bank corneal buttons (mean age, 73.6 years) were included. Ultraviolet A collagen cross-linking was performed postmortem on 3 corneas with the standard protocol involving epithelial debridement and 4 corneas by the transepithelial approach. One cornea served as a control. Corneal nerves were evaluated using confocal microscopy and acetylcholinesterase histology. RESULTS Confocal microscopy demonstrated the absence of subbasal nerves in corneas treated by the standard technique. These nerves were preserved in corneas treated by the transepithelial approach. Stromal nerves were visible in both groups. Histology of corneas treated by the standard technique revealed localized swellings of the stromal nerves with disruption of axonal membrane and loss of axonal continuity within the treatment zone. These changes were absent in corneas treated by the transepithelial approach. CONCLUSIONS This study highlights the immediate effects of collagen cross-linking on the corneal nerves in an ex vivo model. The absence of subbasal nerves in the early phase of treatment appears to be attributable mainly to mechanical removal of epithelium, rather than ultraviolet light-induced damage. Localized swelling of the stromal nerves was the main difference between the 2 treatment protocols. Further research on laboratory animals would be necessary to verify these changes over a specified time course without the super-addition of postmortem changes.

Corneal nerve aberrations in bullous keratopathy.

PURPOSE To study the corneal nerves in patients with chronic bullous keratopathy. DESIGN Prospective observational case series with histologic evaluation. METHODS We studied 25 eyes of 25 bullous keratopathy patients of different etiologies (17 female, 8 male; mean age, 76.3 years) as well as 6 eyes of 6 normal control subjects (5 male, 1 female; mean age, 38 years). All subjects were scanned by laser scanning confocal microscope. Five corneal buttons obtained following penetrating keratoplasty from 5 of the above patients and 6 normal control corneal buttons were stained as whole mounts with acetylcholinesterase (AChE) method for corneal nerve demonstration and scanned in multiple layers with digital pathology scanning microscope. RESULTS The density, branching pattern, and diameter of sub-basal nerves were significantly lower in corneas with bullous keratopathy compared with normal corneas (density: 4.42 ± 1.91 mm/mm(2) vs 20.05 ± 4.24 mm/mm(2); branching pattern: 36.02% ± 26.57% vs 70.79% ± 10.53%; diameter: 3.07 ± 0.64 μm vs 4.57 ± 1.12 μm). Aberrations such as localized thickenings or excrescences, abnormal twisting, coiling, and looping of the (mid) stromal nerves were observed in the study group both by in vivo confocal microscopy and on histology. CONCLUSIONS Striking alterations in corneal innervation are present in corneas with bullous keratopathy that are unrelated to any specific etiology of bullous keratopathy. This study provides histologic confirmation of novel in vivo confocal microscopy findings related to corneal nerves in bullous keratopathy.

Efficacy, predictability, and safety of wavefront-guided refractive laser treatment: Metaanalysis

PURPOSE: To compare the efficacy, predictability, safety, and induced higher‐order aberrations (HOAs) between wavefront‐guided and non‐wavefront‐guided ablations. SETTING: Division of Ophthalmology and Visual Sciences, University of Nottingham, Nottingham, United Kingdom. DESIGN: Metaanalysis. METHODS: The Cochrane Central Register of Controlled Trials, PubMED, and EMBASE were searched for randomized controlled trails. Trials meeting the selection criteria were quality appraised and data extracted by 2 independent authors. Measures of association were pooled quantitatively using metaanalytical methods. Comparison between wavefront‐guided and non‐wavefront‐guided ablations was measured as pooled odds ratios (ORs) or weighted mean differences. The pooled ORs and 95% confidence intervals (CIs) were computed for efficacy, safety, and predictability. The weighted mean difference and 95% CIs were used to compare induced HOAs. RESULTS: Eight trials involving 955 eyes were included. After wavefront‐guided LASIK, the pooled OR of achieving uncorrected distance visual acuity (UDVA) of 20/20 (efficacy) was 1.10 (95% CI, 0.66‐1.83; P=.72), the pooled OR of achieving a result within ±0.50 diopter of intended target (predictability) was 1.03 (95% CI, 0.60‐1.75; P=.92), and the weighted mean difference in induced HOAs was −0.09 (95% CI, −0.17 to −0.01; P=.04). No study reported loss of 2 or more lines of Snellen acuity (safety) with either modality. CONCLUSIONS: Metaanalysis showed no clear evidence of a benefit of wavefront‐guided over non‐wavefront‐guided ablations. However, there was a lack of standardized reporting of UDVA better than 20/20, which might mask an advantage in wavefront‐guided treatment. With high preexisting HOAs, wavefront‐guided has advantages over non‐wavefront‐guided treatment. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Correlation of central and peripheral corneal thickness in healthy corneas

PURPOSE To study the thickness profile of the normal cornea in order to establish any correlation between central and peripheral points. METHODS Sixty-seven eyes of 40 patients were subjected to central corneal thickness measurement (CCT) with an ultrasound pachymeter (UP) and corneal thickness mapping with the Oculus Pentacam. The corneal apex thickness (CAT), pupil centre thickness (recorded as CCT and corresponded to CCT of UP) and thickness at the thinnest location (CTL) were obtained and compared with each other. Corneal thickness data at 3 mm and 7 mm temporally, nasally, superiorly and inferiorly from the corneal apex were obtained. The mean corneal thickness values along the 2, 4, 6, 8 and 10 mm diameter concentric circles, with the CTL as the centre, were also obtained. The above data at different points were statistically correlated. RESULTS There was no significant difference between CCT readings measured by UP and Pentacam (P=0.721). There was high positive correlation between the CAT values and the thickness at 3 mm (R≥0.845, P<0.001) and at 7 mm points (R≥0.654, P<0.001). A gradual increase in thickness was noted from the centre to the periphery with a high positive correlation between the CTL values and the mean thickness at the circles of 2, 4, 6, 8 and 10 mm (R≥0.635, P<0.001). CONCLUSION The results suggest that central corneal thickness can serve as a good guide for predicting peripheral thickness. For surgical procedures specifically undertaken at mid-peripheral and peripheral zones, the actual measurements at the site of surgery may confer some advantage.

The morphologic characteristics of corneal nerves in advanced keratoconus as evaluated by acetylcholinesterase technique.

PURPOSE To study the morphologic characteristics of corneal nerves in patients with advanced keratoconus using the acetylcholinesterase technique in corneal whole mounts. DESIGN Prospective, observational case series. METHODS Fourteen corneal buttons from 14 keratoconic patients (9 males and 5 females; mean age, 34.3 years) who had undergone keratoplasty for advanced keratoconus and 6 corneal buttons from 6 normal corneas were included. Whole mounts were stained for acetylcholinesterase and were scanned with a novel digital pathology scanning microscope. RESULTS Seventy-one percent of keratoconic corneas demonstrated central stromal nerve changes, which included thickening, tortuosity, nerve spouting, and overgrowth. The nerve changes ranged from early to extensive and could be separated into 3 different grades. The central stromal nerves were abnormally thicker (18.9 ± 14.7 μm) than in controls (8.11 ± 3.31 μm; P < .001). The thickness of peripheral stromal nerves (12.6 ± 3.1 μm) was similar to that of controls (14.86 ± 5.60 μm; P = .072). Subbasal nerves showed changes in the form of loss of radial orientation and increased tortuosity, especially at the cone apex. At the cone base, a concentric arrangement of subbasal nerves was found in 43% of cases. Localized thickenings of subbasal nerves also were observed at their origin from the bulbous terminations of sub-Bowman nerves. The terminal bulbs, too, were enlarged. The mean diameter of the subbasal nerves in keratoconus (4.11 ± 0.60 μm) did not differ from that of the controls (4.0 ± 0.61 μm; P = .422). CONCLUSIONS This study provides additional histologic evidence of the involvement of corneal nerves in keratoconus and suggests further that they may play a role in the pathophysiologic factors and progression of the disease.

Profile of sight-threatening infectious keratitis: a prospective study.

Purpose:  To prospectively study patients presenting with sight‐threatening corneal ulcers with a view to identify the predisposing factors, causative organisms, clinical signs and treatment outcomes.