Fiona Carley

Trends in the Indications for Corneal Graft Surgery in the United Kingdom: 1999 Through 2009

OBJECTIVE To examine trends in the indications for corneal graft surgery in the United Kingdom. METHODS National Health Service Blood and Transplant data were analyzed for keratoplasty operations performed in the United Kingdom between April 1, 1999, and March 31, 2009, distinguishing the type of graft and the surgical indication. RESULTS The total number of annual keratoplasty operations increased from 2090 in 1999-2000 to 2511 in 2008-2009. Among these, the annual number of grafts performed for endothelial failure increased from 743 (35.6%) in 1999-2000 to 939 (37.4%) in 2008-2009. The performance of penetrating keratoplasty (PK) for endothelial failure decreased from 98.3% of all grafts in 1999-2000 to 46.6% of all grafts in 2008-2009, while the performance of endothelial keratoplasty increased from 0.3% of all grafts in 1999-2000 to 51.2% of all grafts in 2008-2009. The annual number of grafts performed for keratoconus increased from 514 (24.6%) in 1999 to 564 (22.5%) in 2008-2009. The performance of PK for keratoconus decreased from 88.4% of all grafts in 1999-2000 to 57.1% of all grafts in 2008-2009, while the performance of deep anterior lamellar keratoplasty increased from 8.8% of all grafts in 1999-2000 to 40.1% of all grafts in 2008-2009. The number of annual regraft operations increased from 249 (11.9%) in 1999-2000 to 401 (16.0%) in 2008-2009, most commonly for endothelial failure. In 2008-2009, PK regrafts (78.1%) far outnumbered endothelial keratoplasty regrafts (17.0%). CONCLUSIONS Endothelial failure is the most common indication for keratoplasty in the United Kingdom, and endothelial keratoplasty is performed more commonly than PK for this indication. The number of grafts performed for pseudophakic bullous keratopathy has remained stable, while the number of grafts performed for Fuchs endothelial dystrophy is likely to continue increasing. Keratoconus is the second most common indication for keratoplasty, and deep anterior lamellar keratoplasty numbers are approaching those for PK. Regraft surgery is the third most common indication for keratoplasty, required in most cases because of endothelial failure.

Trends in corneal graft surgery in the UK

Aims The aims of this study were to examine trends over time and regional variation in rates of corneal graft surgery in the UK. Methods The hospital in-patient enquiry (HIPE) and hospital episode statistics (HES) were analysed for keratoplasty admissions in England from 1971 to 2006. NHS Blood and Transplant (NHSBT) data were analysed for keratoplasty operations in the UK from 1999 to 2009. Results Annual rates of penetrating keratoplasty (PK) under HIPE and HES increased from 0.7 per 100 000 population (1971) to 3.9 (1992), then decreased to 3.1 (2006). Rates of lamellar keratoplasty (LK) increased from 0.1 (1971) to 0.9 (2006). Annual PK operations under NHSBT decreased from 1901 (1999/00) to 1473 (2008/9). Over the same period, deep anterior lamellar keratoplasty operations increased from 91 to 327 per year, while endothelial keratoplasty operations increased from 2 to 569 per year. Geographical analysis showed a wide variation across local authority areas in rates of keratoplasty around 1998–2004, especially for LK. Conclusion The total number of corneal graft operations performed in the UK has increased slowly over the past decade. The proportion of lamellar versus penetrating keratoplasty has increased, with LK performed at the highest rates in specialist centres distributed across the UK.

Biomechanical Properties of Human Corneas Following Low- and High-Intensity Collagen Cross-Linking Determined With Scanning Acoustic Microscopy

PURPOSE To assess and compare changes in the biomechanical properties of the cornea following different corneal collagen cross-linking protocols using scanning acoustic microscopy (SAM). METHODS Ten donor human corneal pairs were divided into two groups consisting of five corneal pairs in each group. In group A, five corneas were treated with low-fluence (370 nm, 3 mW/cm(2)) cross-linking (CXL) for 30 minutes. In group B, five corneas were treated with high-fluence (370 nm, 9 mW/cm(2)) CXL for 10 minutes. The contralateral control corneas in both groups had similar treatment but without ultraviolet A. The biomechanical properties of all corneas were tested using SAM. RESULTS In group A, the mean speed of sound in the treated corneas was 1677.38 ± 10.70 ms(-1) anteriorly and 1603.90 ± 9.82 ms(-1) posteriorly, while it was 1595.23 ± 9.66 ms(-1) anteriorly and 1577.13 ± 8.16 ms(-1) posteriorly in the control corneas. In group B, the mean speed of sound of the treated corneas was 1665.06 ± 9.54 ms(-1) anteriorly and 1589.89 ± 9.73 ms(-1) posteriorly, while it was 1583.55 ± 8.22 ms(-1) anteriorly and 1565.46 ± 8.13 ms(-1) posteriorly in the untreated control corneas. The increase in stiffness between the cross-linked and control corneas in both groups was by a factor of 1.051×. CONCLUSIONS SAM successfully detected changes in the corneal stiffness after application of collagen cross-linking. A higher speed-of-sound value was found in the treated corneas when compared with the controls. No significant difference was found in corneal stiffness between the corneas cross-linked with low- and high-intensity protocols.

The suitability of corneas stored by organ culture for penetrating keratoplasty and influence of donor and recipient factors on 5-year graft survival.

PURPOSE To determine the impact of donor factors on the suitability of corneas stored by organ culture for penetrating keratoplasty (PK) and the influence of donor and recipient factors on 5-year survival of first PK. METHODS Logistic regression analyses were carried out to determine the influence of donor factors on, respectively, the risk of microbial contamination during organ culture, the suitability of corneas for PK (endothelial cell density ≥ 2200 cells/mm(2)), and the quality of corneas (endothelial cell density ≥ 2500 cells/mm(2)). Only one cornea, randomly selected, from each donor was included in these analyses. A Cox regression analysis was used to determine the influence of donor and recipient factors on 5-year PK survival. RESULTS Risk of contamination (n = 8317): Causes of donor death including infection, respiratory disease, and cancer all increased the risk of contamination during organ culture (P < 0.0001). Suitability for PK and endothelial quality (n = 7107): Donor age (P < 0.0001) and storage time in organ culture (P < 0.0001) were the principal factors affecting suitability and quality. Death to enucleation and enucleation to processing times had little influence. Corneas from organ donors were more likely to be suitable for PK (P = 0.0003). Five-year graft survival (n = 3014): Graft survival was dominated by the indication for PK (P < 0.0001). Allograft rejection was also a major risk factor for failure (P < 0.0001). The only donor factor affecting survival was sex (P = 0.008). CONCLUSIONS Donor age and storage time but not postmortem times influenced the suitability of corneas for PK. The indication for PK and other recipient factors were the main predictors of graft failure.

Residual corneal stroma in big-bubble deep anterior lamellar keratoplasty: a histological study in eye-bank corneas

Aim To determine if residual corneal stroma remains on the recipient posterior lamella in big-bubble deep anterior lamellar keratoplasty (DALK). Methods Pneumodissection using the big-bubble technique was carried out on eye-bank corneas mounted on an artificial anterior chamber. Samples that had a successful big-bubble formation were sent for histological evaluation to determine if any residual stroma remained on the Descemet membrane (DM). Results Big-bubble formation was achieved in 32 donor corneas. Two distinct types of big-bubble were seen: the bubble had either a white margin (30 corneas) or a clear margin (two corneas). The posterior lamellae of all the white margin corneas showed residual stroma on DM with a mean central thickness of 7.0 μm (range 2.6–17.4 μm). The clear margin corneas showed no residual stroma on DM. Conclusion It should no longer be assumed that big-bubble DALK, where the bubble has a white margin, routinely bares DM. True baring of DM may only occur with the less commonly seen clear margin bubble.

An in depth analysis of histopathological characteristics found in keratoconus.

Aims: The aims of this study were to re-assess the histopathology of the disease by introducing more modern measuring techniques and to determine if axial stromal thinning, which is the most apparent change, is related to the other alterations observed. Methods: Recipient keratoconic corneas from 36 patients following corneal transplantation were studied. Haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were used to identify breaks in Bowmans layer and Descemets membrane. Thickness of corneal layers was measured by Leica QWin software. Epithelial and stromal thickness were measured in each sample at the periphery of the corneal button and at the area of maximal stromal thinning. The presence of apoptotic cells in Bowmans layer breaks was detected by terminal deoxynucleotidyl transferase mediated dUTP-X nick end labelling. Results: In all 36 corneal samples the central stroma, at the apex of the cone, was thinner than the peripheral. There was a negative correlation between central stromal and central epithelial thickness (p = 0.009). Bowmans layer breaks were found in 92% of corneas. Apoptotic cells were detected at the level of Bowmans breaks membrane. We found a positive correlation between epithelial thickness and the number of Bowmans layer breaks (p = 0.009 for central epithelial thickness and p = 0.003 for peripheral epithelial thickness). Descemets membrane deformities were observed in 19% of corneas and central stromal thickness of these corneas was significantly less than corneas without breaks (p = 0.006). Conclusions: There are various different histopathological features associated with keratoconus and some of them are very subtle and not very well studied. Accurate measurements also suggest some correlations between them. Stromal thinning is associated with the number of breaks in Descemets membrane, but it is the thickening of the epithelium which is associated with breaks in Bowmans layer.

Scanning Acoustic Microscopy for Mapping the Microelastic Properties of Human Corneal Tissue

Abstract Purpose: To assess the feasibility of applying scanning acoustic microscopy (SAM) on UV cross-linked corneal tissue for mapping and analyzing its biomechanical properties. Materials and Methods: Five corneal pairs (10 corneas) were used. In each pair, one cornea was cross-linked (epithelium removed, riboflavin application for 45 min and UVA irradiation for 30 min) and the contralateral control cornea was epithelial debrided and treated only with riboflavin for 45 min. Histological sections were prepared and their mechanical properties were examined using SAM. A line profile technique and 2D analysis was used to analyze the mechanical properties of the corneas. Then the corneal paraformaldehyde and unfixed sections were examined histologically using hematoxylin and eosin (H&E) staining. Results: In the frozen fresh corneal tissue, the speed of sound of the treated corneas was 1672.5 ± 36.9 ms−1, while it was 1584.2 ± 25.9 ms−1 in the untreated corneas. In the paraformaldehyde fixed corneal tissue, the speed of sound of the treated corneas was 1863.0 ± 12.7 ms−1, while it was 1739.5 ± 30.4 ms−1 in the untreated corneas. The images obtained from the SAM technique corresponded well with the histological images obtained with H&E staining. Conclusion: SAM is a novel tool for examining corneal tissue with a high spatial resolution, providing both histological and mechanical data.

Donor preparation using pneumatic dissection in endothelial keratoplasty: DMEK or DSEK?

Purpose: To determine if residual stroma remains on the Descemet membrane when pneumatic dissection is used to prepare donor tissue for endothelial keratoplasty. Methods: Pneumatic dissection using a posterior peripheral needle insertion was carried out on 5 eye bank corneas. Samples were then sent for histological analysis. Results: A thin layer of stroma remained on the Descemet membrane in all the samples. The average central stromal thickness was 12.4 &mgr;m (range 6.5–20.0 &mgr;m). Conclusions: Endothelial keratoplasty using pneumatic dissection to prepare donor tissue should be considered a form of Descemet stripping endothelial keratoplasty and not Descemet membrane endothelial keratoplasty. If future studies show excellent visual results using pneumatic dissection for endothelial keratoplasty, then removal of all donor stroma may be unnecessary.

Treatment of superior limbic keratoconjunctivitis with a unilateral bandage contact lens

The typical patient with superior limbic keratoconjunctivitis (SLK) is a woman aged between 20 and 60 years of age with chronic red and irritable eyes.1 Although both eyes are usually affected, the condition maybe asymmetrical.1 After episodes of exacerbation and remission it usually resolves. The patient may also have abnormal thyroid function.2 SLK has been treated with silver nitrate or thermal cauterisation of the superior bulbar conjunctiva, pressure patching, and large diameter bandage contact lenses (BCL), topical trans-retinoic acid 0.1%, and recession or resection of the superior bulbar conjunctiva.1, 3 Over 50% of patients with SLK are said to have keratoconjunctivitis sicca4 and recently upper punctal plugs have been used to treat SLK.5 We report two cases in which a unilateral BCL wear ameliorated the symptoms of bilateral SLK and a possible explanation is discussed. ### Case 1 A 38 year old woman presented with a 3 month history of irritable photophobic eyes that were unresponsive to preserved lubricants. Her right eye was amblyopic. On systemic review she reported weight loss, heat intolerance, and insomnia. Slit lamp examination revealed bilateral superior conjunctival hyperaemia, superior punctate epithelial erosions, and four to five filaments and micropannus …

Dissection plane of the clear margin big-bubble in deep anterior lamellar keratoplasty.

To the Editor: The big-bubble technique of deep anterior lamellar keratoplasty (DALK) involves injection of air into the cornea to separate an anterior and a posterior lamella. In the original description, bubble formation is seen as an advancing white band. It has subsequently been widely assumed in the literature that the cleavage plane in this instance is between stroma and the Descemet membrane (DM). Later, a second type of big-bubble was described in which a distinctly different type of bubble forms that has a clear margin and has an appearance similar to that of an air bubble in the anterior chamber. The cleavage plane in this type of bubble has been assumed to be intra-DM. However, recent studies by our group and another group have suggested that the cleavage plane in the big bubble that forms with the white band is actually intrastromal. Our study also examined 2 cases of the clear margin bubble and concluded it was bare DM but could not comment on the cleavage plane because electron microscopy (EM) was not performed. We have subsequently examined 2 donor corneas in which clear margin bubbles had formed to further examine this cleavage plane. Big-bubble DALK was performed as per our previous study. Two of 41 corneas had clear margin bubbles and were sent for analysis. The posterior lamella in one case, and the anterior and posterior lamellae in the other case were examined under light microscopy and EM to determine if DM was intact. In both cases, light microscopy suggested that the DM in both posterior lamellae were intact (Fig. 1). The anterior lamella showed bare stroma on its posterior surface with no sign of attached DM to suggest an intra-DM cleavage plane. In addition, EM revealed intact DM with the anterior banded and posterior non-banded zones present on both posterior lamellae (Fig. 2A). EM did not reveal any DM attached to the stroma of the anterior lamella (Fig. 2B). The cleavage plane in these donor cornea clear margin bubbles was between stroma and DM and not intra-DM. An obvious limitation of this study is the use of donor corneas and the small sample size. However, as mentioned in our previous study, the findings seen were identical to those observed clinically. Also, a clear margin bubble is an uncommon occurrence, making studies difficult. We would encourage surgeons to send the anterior lamella for histological assessment in cases of a clear margin bubble. Analysis of the stroma for residual DM would provide further information on the cleavage plane in this situation. It would appear that the current paradigm that big-bubble DALK is a DM-baring procedure, with an intraDM cleavage plane occurring when the bubble has a clear margin, is not evidence based. Until further studies prove otherwise, residual stroma should be assumed to be present in big-bubble DALK, unless the bubble forms with a clear margin. In the latter situation, the term “intra-DM bubble” should be discarded unless it can be shown that this cleavage plane occurs consistently in this situation, something our study sheds doubt on. These distinctions are important. Residual stroma could be beneficial, FIGURE 1. Periodic acid-Schiff–stained histological section (·600) of a posterior lamella from a clear margin bubble in a donor cornea showing intact DM and attached corneal endothelial cells (arrows) on one surface.