Usama Fares

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.

Outcomes of deep anterior lamellar keratoplasty following successful and failed ‘big bubble’

Aim The most popular technique for deep anterior lamellar keratoplasty (DALK) is the ‘big bubble’ (BB) technique wherein air is injected in the cornea to create a bubble that separates Descemets membrane (DM) from the stroma. An attempt to create a BB often results in the cornea being filled with numerous small bubbles without the formation of a BB. Manual dissection is then required to complete the procedure. The aim of the study is to compare these two groups, successful BB versus failed bubble (FB) dissection to determine whether the clinical outcomes were different. Methods In this retrospective comparative study, 46 patients out of 52 who underwent DALK for various corneal stromal diseases such as keratoconus, stromal dystrophy or corneal scarring (caused by different conditions) were included in the analysis. BB was achieved in 25 patients and in the remaining 21 patients a BB separation of the DM was not possible necessitating manual lamellar dissection of stroma to get as close to the DM as possible. Results The authors compared best-corrected visual acuity, contrast sensitivity, astigmatism, interface densitometry and Scheimpflug pachymetry in the two groups. Postoperative corneal thickness was higher in the ‘small bubbles’ group (mean 628.9 vs 564.1 μm; p<0.0005), but there was no significant difference in best-corrected visual acuity, astigmatism, contrast sensitivity and densitometry between the groups. Conclusions In DALK, manual lamellar dissection is a reasonable alternative when BB separation of the DM is not achieved.

Management of post-keratoplasty astigmatism.

UNLABELLED Post-keratoplasty astigmatism remains a challenge for corneorefractive surgeons. While maintaining a healthy graft is the most crucial issue in keratoplasty procedures, astigmatism is a limiting factor in the visual rehabilitation of otherwise successful corneal grafts. The management of post-keratoplasty astigmatism takes place at 2 stages: when sutures are still present at the graft-host junction and when all sutures have been removed. Excessive suture-in post-keratoplasty astigmatism is usually managed by selective suture manipulation, ie, suture adjustment and/or suture removal along the steep meridian of astigmatism. A small amount of suture-out post-keratoplasty astigmatism can be managed by spectacles. Higher magnitudes of astigmatism can be addressed by contact lenses or surgical intervention, such as relaxing and compressing procedures. Laser lamellar refractive surgery can also be used to manage post-keratoplasty astigmatism, and toric phakic intraocular lenses have recently been recommended. In this review, we discuss the etiology and management of post-keratoplasty astigmatism and provide recommendations and tips to minimize it. FINANCIAL DISCLOSURE No author has a financial or proprietary interest in any material or method mentioned.

In vivo confocal microscopic findings in patients with limbal stem cell deficiency

Aim To describe in vivo confocal microscopy (IVCM) findings in patients with limbal stem cell deficiency (LSCD). Methods 23 eyes of 17 consecutive patients suffering from LSCD were included in this study. A detailed examination by IVCM was performed in addition to a routine slit-lamp biomicroscopy. Size and density of corneal epithelial and conjunctival epithelial cells on cornea were measured and statistically analysed using SPSS version 8.0 software. Results were compared with histology in select cases. Results Anatomical and morphological differences were observed between normal corneal cells and conjunctival epithelial cells on cornea. Size and density differences reached statistically significant levels between the normal corneal cells and the conjunctival epithelial cells on cornea (p<0.01). Goblet cells were visible throughout the conjunctivalised corneal epithelium in eight eyes. Several IVCM features could be correlated with histology in six of our patients. Conclusions A number of features were demonstrated by laser IVCM in patients presenting clinically with LSCD. Some of these features were corroborated with features observed on histological examination of tissue samples.

In vivo confocal microscopic features of normal limbus

Aim To describe in vivo confocal microscopy (IVCM) features of the limbus in normal eyes as related to the palisades of Vogts. Methods 46 eyes of 29 consecutive volunteers were recruited in this observational study. A detailed examination by IVCM was performed in addition to a routine slit-lamp biomicroscopy. Size and density of corneal and limbal epithelial cells were measured and statistically analysed using SPSS version 8.0 software. Results Anatomical and morphological features were noted between corneal and limbal cells. Size and density differences reached to significant levels (p<0.05). Different shapes of palisades of Vogt have been described clearly by confocal microscope. Cell-like structures were observed in the peripheral end of the palisades which might represent limbal stem cell crypts. Conclusions Laser IVCM can be used to establish the features of the normal limbus. The identified features demonstrate quantitative changes in the basal epithelium between the limbus and the central cornea and morphological differences between pigmented or non-pigmented studied subjects. Further studies should be performed to correlate with histology the possible crypts which were observed in this study.

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.

Re-treatment after laser in situ keratomileusis for correction of myopia and myopic astigmatism

Aim: To evaluate the results of laser in situ keratomileusis (LASIK) re-treatment for under correction or regression after primary LASIK procedures for myopia and myopic astigmatism. Methods: A prospective evaluation of 360 consecutive LASIK-treated eyes, for myopia and/or myopic astigmatism, 32 eyes of 34 patients were retreated and followed at 3, 6 and 12 months post-retreatment. Re-treatment was performed by lifting the original flap after cutting the epithelium around the flap edge with a fine needle. Standard ablation was performed based on the patient’s residual refraction. Results: 9.4% of eyes required retreatment. Prior to re-treatment the mean manifest spherical equivalent (SE) was −0.99 (SD 1.48) D (range −0.75 to −2.63). The mean sphere was −0.79 (1.20) D (range −2.50 to −0.50), and the mean cylinder was −0.90 D (1.14) D (from −2.75 to 1.25). At 1-year follow-up 56% of the eyes were within ±0.50 D SE, and 78% were within ±1.00 D SE. 78% of the eyes examined at 1-year post-re-treatment managed unaided vision of 6/9 or better. Peripheral epithelial ingrowth not requiring treatment developed in two eyes. Second re-treatment for regression was performed in one eye. A significant correlation was found between the refractive regression and each of the following: preoperative refraction, attempted correction and ablation depth. Conclusion: LASIK re-treatment for residual myopia, by lifting the original flap, is an effective option. Refractive results are fairly predictable, and refraction stabilises by 3 months after re-treatment. Lifting the corneal flap after cutting the epithelium on the flap edges is easy to perform and has a very low incidence of epithelial ingrowth.