In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review.

The exponential evolution of in vivo confocal microscopy (IVCM) has led to a significant enhancement in our knowledge of the living cornea in both its physiological and pathological states. Studies using white light and coherent light-based IVCM have enabled detailed quantitative analysis of sub-basal nerve parameters, and have also resulted in the elucidation of the two-dimensional architecture of the normal corneal sub-basal nerve plexus. However, accurate and repeatable methods for quantitative analysis of stromal nerves imaged by IVCM remain to be developed. The effect of corneal surgery on central corneal nerves has been well documented in many IVCM studies, and these studies provide an indication of the regenerative capacity of corneal nerves. IVCM has also clearly demonstrated the involvement of corneal nerves in diseases such as keratoconus, although it remains unclear whether these alterations are a cause of, or occur secondary to, the disease process. IVCM has also been proposed as non-invasive method of accurately diagnosing and assessing the progression of diabetic neuropathy, highlighting the potential application of this technique as an indicator of systemic disease. This review consolidates our knowledge of how IVCM has contributed significantly to our greater understanding of corneal nerves in the living human cornea in health and disease.

Identifying relationships between tomography-derived corneal thickness, curvature, and diameter and in vivo confocal microscopic assessment of the endothelium in healthy corneas of young adults.

PURPOSE: Despite the importance of a healthy endothelial layer in anterior segment surgery, the possible influence of corneal parameters on endothelial cell density (ECD) has largely been ignored in the young adult eye. This study investigated the possible associations between corneal tomographic parameters and ECD values in young adults. METHODS: Subjects aged 21-30 years, with normal corneas were recruited. Mean ECD, mean cell area (MCA), coefficient of variation for cell area (COVA), and proportion of hexagonal cells were derived by in vivo confocal microscopy. The Orbscan II system was used to measure corneal parameters including: thickness, horizontal corneal diameter, corneal curvature, anterior and posterior elevation, and eccentricity. RESULTS: Sixty-two subjects (42 female, 20 male) were included (mean age 25+/-3 years). Overall mean ECD was 3169+/-309 cells/mm(2) with no differences between genders. Mean percentage of hexagonality was 53+/-5%, male subjects (55%) had a higher percentage of hexagonal cells than female subjects (51%) (P=0.02). Central corneal thickness (CCT) was 529+/-43 microm. Central ECD was significantly correlated with CCT (Pearson's r=0.26, P=0.04). However, horizontal corneal diameter (r=0.19, P=0.14), anterior corneal curvature (r=-0.07, P=0.6), and posterior corneal curvature (r=-0.07, P=0.6) were not correlated with ECD or percentage of hexagonality. There was no statistically significant association between anterior chamber depth (3.6+/-0.3 mm) and ECD (r=0.15, P=0.3). CONCLUSION: Corneal thickness is related to ECD in normal young adult eye, with lower ECD values identified in thinner corneas; however, corneal diameter and corneal curvature do not have a significant correlation with ECD.

The Dundee University Scottish Keratoconus Study II: a prospective study of optical and surgical correction.

AIM: To investigate and correlate optical correction, and progression to penetrating keratoplasty (PKP), with the corneal, refractive, topographic and familial characteristics of subjects with keratoconus, within the Tayside region of Scotland. METHOD: Prospective, observational, longitudinal study design. Two hundred subjects with keratoconus were enrolled into the Dundee University Scottish Keratoconus Study (DUSKS) and were assessed during a 4-year period using standardised clinical assessment, computerised corneal topography and questionnaires. RESULTS: Keratoconic subjects in this study wore rigid contact lenses (90.6%) for longer than 12 hours per day (81%), 7 days a week (91%) and achieved a very good level of Snellen visual acuity (97%, > or =6/9). Corneal staining was observed in the majority of corneas (71%), although only a small percentage of subjects reported major problems of: discomfort (18%), hyperaemia (16%), or the lens falling out (4%). Poor visual acuity was the main reason (79%) for undergoing PKP usually in the latter part of the third decade of life, approximately a decade after diagnosis. During the study period 4% of eyes progressed to PKP. Only a small percentage of eyes (9.5%) required no visual correction postoperatively. CONCLUSION: The main mode of visual rehabilitation for keratoconus was rigid contact lenses, which were mostly worn successfully with good visual acuity. During the study period a small minority of keratoconics progressed to corneal graft surgery. It is advisable to emphasise that postoperatively refractive correction will be required in the majority of these cases.

Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study.

AIMS: To quantify and establish baseline normative data for age-related differences in cellular and innervation density in the normal, healthy, human cornea using laser scanning in vivo confocal microscopy. METHODS: Cross-sectional study of 85 normal subjects assessed via corneal topography and laser scanning in vivo confocal microscopy. RESULTS: Mean age was 38+/-16 years (range 18-87 years) and 60% of subjects were female. Anterior keratocyte density declined by 0.9% per year (r = -0.423, p<0.001), posterior keratocyte density declined by 0.3% per year (r = -0.250, p = 0.021) and endothelial cell density declined by 0.5% per year (r = -0.615, p<0.001). Sub-basal nerve fibre density declined by 0.9% per year (r = -0.423, p<0.001). No association was observed between age and basal epithelial cell density, or between age and central corneal thickness, corneal astigmatism or horizontal corneal diameter (p>0.05). No association was observed between subject gender and corneal cell or innervation density. CONCLUSIONS: Using laser scanning in vivo confocal microscopy this study highlights a significant, and relatively linear, reduction in keratocyte and endothelial cell density with increasing subject age. Interestingly, corneal sub-basal nerve fibre density also significantly decreases with increasing age. In vivo laser scanning confocal microscopy provides a safe, non-invasive method for the establishment of normative data and assessment of alterations in human corneal microstructure following surgery or disease processes.

The Auckland Cataract Study: 2 year postoperative assessment of aspects of clinical, visual, corneal topographic and satisfaction outcomes.

AIM: To assess clinical, visual, computerised corneal topographic, and subjective satisfaction with visual acuity, in a cohort of subjects 2 years after phacoemulsification surgery in a public hospital in New Zealand. METHODS: Prospective study of a representative sample of 97 subjects (20%) randomly selected from 480 subjects in the original Auckland Cataract Study (ACS) cohort. The clinical assessment protocol was identical to the ACS and included an extensive questionnaire to enable direct comparisons to be made between the two groups. RESULTS: The study population was predominantly female (66%) with a mean age of 76.3 (SD 9.9) years. New systemic and ocular disease affected 18.4% and 10.3% of subjects respectively, and 10.3% required referral to either a general practitioner (2.1%) or ophthalmologist (8.2%). Mean best spectacle corrected visual acuity (BSCVA) was 0.2 (0.2) logMAR units (6/9 Snellen equivalent), with mean spherical equivalent -0.37 (1.01) dioptres (D) and astigmatism -1.07 (0.70) D 2 years postoperatively, compared to mean BSCVA 0.1 (0.2) logMAR units (6/7.5 Snellen equivalent), spherical equivalent -0.59 (1.07) D, and astigmatism -1.14 (0.77) D 4 weeks after surgery. 94.9% of subjects retained a BSCVA of 6/12 or better, irrespective of pre-existing ocular disease. The overall posterior capsule opacification (PCO) rate was 20.4% and this was visually insignificant in all but 3.1% of eyes that had already undergone Nd:YAG posterior capsulotomy. Orbscan II elevation technology demonstrated corneal stability 2 years after uncomplicated phacoemulsification. Although corneal astigmatism was eliminated in approximately half of the subjects 1 month postoperatively, astigmatism showed a tendency to regress towards the preoperative level with local corneal thickening at the site of incision 2 years after cataract surgery. Of fellow eyes, 61.2% had undergone cataract surgery. Overall, 75.3% of subjects were moderately to very satisfied with their current level of visual acuity. CONCLUSION: Two years after cataract surgery subjects are generally satisfied with their current level of vision and distance BSCVA is 6/12 or better in the majority of eyes. Although only a minority of eyes develop sufficient PCO to require capsulotomy 10.3% of eyes develop new vision threatening ocular pathology.

The effects of corneal parameters on the assessment of endothelial cell density in the elderly eye.

BACKGROUND: The possible impact of corneal thickness, curvature, and size on the measurement of endothelial cell density (ECD) has largely been ignored in the normal eye. The aim of this study was to investigate the possible impact of the main corneal parameters on the analysis of ECD values at the central, superior, and temporal parts of the corneal surface. METHODS: All 75 participants (52 females, 23 males) were assessed as part of a pre-cataract surgery investigation. The mean age was 75.7 (SD 10.9) years. Confocal microscopy was used to measure ECD and the percentage of six sided cells at the central, superior, and temporal parts of the cornea. The Orbscan II topography system was used to measure corneal thickness, topography, and horizontal corneal diameter. RESULTS: The mean central ECD measured was 2488 (SD 301) cells/mm(2), compared with 2525 (SD 505) cells/mm(2) in the temporal cornea and 2639 (SD 398) cells/mm(2) in the superior cornea. The regional differences in ECD were not significant (p>0.14). The central ECD was significantly correlated to the central (mean 0.593 (SD 0.039) mm, p = 0.021) as well as the temporal (0.628 (SD 0.039) mm, p<0.001) and the superior corneal thickness (SD 0.644 (SD 0.048) mm, p = 0.018). The mean corneal curvature at the centre (7.7 (SD 0.34) mm, p = 0.002) as well as 3 and 5 mm from the apex was significantly related to ECD (p = 0.008 and p = 0.009, respectively). CONCLUSIONS: The study suggests that in an older population, lower ECD values would be expected in thinner and/or steeper corneas.

Severe infective keratitis leading to hospital admission in New Zealand.

AIM: To identify key risk factors and the management and outcome of severe infective keratitis leading to public hospital admission in New Zealand. METHODS: Over a 2 year period, all admissions of presumed infective keratitis to Auckland Hospital were identified. The clinical records of all 103 cases were retrospectively reviewed with respect to clinical features, risk factors, management, and outcomes. RESULTS: The mean time from first symptoms or signs and presentation to hospital was 8.9 (SD 15.5) days. The majority of subjects, 88%, had at least one of the risk factors commonly associated with infective keratitis including previous ocular surgery (30%), contact lens wear (26%), topical corticosteroid use (25%), and ocular trauma (24%). Corneal scraping was performed in 92% and of a total of 105 scrapes, 71% were positive. Bacteria were isolated in all these cases, the majority being Gram positive organisms (72%). The most common isolates identified were coagulase negative Staphylococcus (16%), Propionibacterium acnes (14%), Staphylococcus epidermidis (11%), and Streptococcus pneumoniae (9%). In addition, yeasts were isolated in 5%, fungi in 4%, virus in 2%, and chlamydia in 1%. Importantly, polymicrobial infection accounted for 33% of culture positive cases. Antimicrobial treatment was changed on the basis of culture results in 17 cases (16.5%). Median initial visual and final best corrected visual acuity was 6/36-6/48 (logMAR 0.86) (IQR 0.39-2.00) and 6/12-6/15 (logMAR 0.360) (IQR 0.15-1.70), respectively. Previous ocular surgery and topical corticosteroid use were significantly associated with poorer visual acuity. The mean hospital stay was 5.8 days and the median 4.0 (IQR 2.0-8.0) days. Longer duration of stay was associated with the presence of hypopyon, larger ulcers, previous ocular surgery, and poor visual acuity. CONCLUSIONS: Infectious keratitis is an important cause of ocular morbidity. A significant proportion of cases have potentially modifiable risk factors. Previous ocular surgery and topical corticosteroid use, in particular, were associated with poorer visual outcomes. Many cases of severe keratitis might be avoided, or their severity reduced, by appropriate education of patients and ophthalmologists.

Comparison of corneal thickness measurements using ultrasound and Orbscan slit-scanning topography in normal and post-LASIK eyes.

PURPOSE: To compare corneal thickness measurements made by ultrasonic and slit-scanning techniques in normal eyes and in eyes after laser in situ keratomileusis (LASIK). SETTING: Corneal Diseases and Excimer Laser Research Unit, University of Dundee, Dundee, Scotland. METHODS: Central corneal thickness (CCT) was measured in 101 eyes of 59 normal subjects and in 30 eyes of 21 post-LASIK patients. Measurements were made with an Orbscan slit-scanning elevation topographer and immediately afterward with an ultrasound pachymeter. RESULTS: The difference in mean CCT between ultrasound (538.0 microm +/- 36.7 [SD]) and Orbscan (566.6 +/- 40.7 microm) pachymetry was statistically significant (P <.001) in the normal eyes; the Orbscan measurement was approximately 28 microm higher than that of the ultrasound pachymeter. The difference in mean CCT between the ultrasound and the slit-scanning techniques was also statistically significant in the post-LASIK eyes (mean values 475.3 +/- 50.3 microm and 461.9 +/- 74.2 microm, respectively; P <.0001). Differences in CCT in individual subjects were much more variable in the post-LASIK eyes than in the normal eyes. The Bland and Altman method for assessing clinical agreement between 2 instruments showed that in 95% of cases, the CCT measurements with both instruments would be within 65 microm in normal eyes and 150 microm in post-LASIK eyes. CONCLUSION: Central corneal thickness measurements were, on average, 28 microm higher with the Orbscan than with the ultrasound pachymeter in normal eyes and 13 microm lower in post-LASIK eyes. The degree of variability within each group indicated that these 2 techniques are not clinically comparable, precluding interchangeable use of their data in planning or assessing corneal surgery.

In vivo confocal microscopy of corneal epithelial ingrowth through a laser in situ keratomileusis flap buttonhole.

We report a case of epithelial ingrowth through a buttonhole 6 months after laser in situ keratomileusis. Elevation topography showed irregular astigmatism and an unreliable pachymetric map. In vivo confocal microscopy showed an epithelial basal cell mosaic with prominent borders and distinct nuclei. No corneal nerves were identified in any image. Cells in the anterior stroma possessed bright, reflective nuclei and appeared to form clusters. The interface between the stromal bed and the flap had formation of nests of fibrotic tissue and epithelial cells.

Safety and predictability of laser in situ keratomileusis enhancement by flap reelevation in high myopia.

PURPOSE: To evaluate the safety and predictability of laser in situ keratomileusis (LASIK) retreatment following primary procedures for high myopia and astigmatism. SETTING: Corneal Diseases and Excimer Laser Research Unit, Department of Ophthalmology, University of Dundee, Dundee, United Kingdom. METHODS: This prospective observational study of retreatment comprised a cohort of 109 eyes having primary LASIK for high myopia and astigmatism with a spherical equivalent (SE) of -9.70 diopters (D) +/- 4.06 (SD). Twenty-four eyes (22%) with an initial myopic SE of -9.83 +/- 3.50 D, a comparable subset of the entire group (P < .05), had retreatment for residual myopia (-3.02 +/- 2.17 D) to improve uncorrected visual acuity (UCVA) by reelevating the corneal flap and ablating the stromal bed. RESULTS: The mean follow-up after retreatment was 12.8 +/- 5.1 months (range 1.5 to 24 months; 19 eyes >/=6 months, 13 eyes > or = 12 months). The mean myopic SE was reduced to +0.53 +/- 0.62 D at 1 week, +0.05 +/- 0.50 D at 1 month, +0.30 +/- 0.50 D at 6 months, and +0.18 +/- 0.42 D at the latest follow-up, 12.8 months. At the latest review, 62% of eyes were within +/-0.50 D of emmetropia and 100% were within +/-1.00 D. The mean refraction did not alter statistically between 1 week and subsequent times. The mean UCVA improved from 6/30 prior to retreatment to 6/9 at the latest follow-up. Uncorrected visual acuity of 6/6 or better, 6/9 or better, and 6/12 or better was achieved by 33.0%, 75.0%, and 95.8% of eyes, respectively. No significant complications that led to a loss of best corrected visual acuity were encountered, although retreatment procedures were more uncomfortable than primary procedures and self-limiting; epithelial ingrowth that did not threaten vision was common, and 2 patients complained of nighttime visual symptoms. CONCLUSIONS: Retreatment of residual myopia by reelevating the flap was relatively safe and predictable, with a low risk of sight-threatening complications. However, longer term studies may be required to detect late complications.

The waiting game: natural history of a cataract waiting list in New Zealand.

AIMS: To identify the demographic and visual function of patients on the reserve waiting list for cataract surgery at a large public hospital within New Zealand and to determine the ultimate outcome of those on a priority-based, rationed, health-care waiting list. METHODS: Patients from a defined geographical population, placed on a reserve waiting list for possible cataract surgery, during the period January 1997 to March 2000, were invited to attend for further clinical assessment and asked to complete a visual assessment questionnaire. RESULTS: Of 193 patients in the pilot study group who had been on the reserve waiting list for a mean of 18.2 +/- 11.6 months (range 0.1-62.7 months), only 94 (49%) were deemed suitable for, and subsequently underwent, surgery in the public sector. Forty-nine (25%) had undergone surgery earlier, the majority of these (84%) in the private sector. A further 23 (12%) patients were deceased, four (2%) declined surgery and in six (3%) cataract surgery was no longer indicated. The remaining 11 (6%) patients could not be traced. Patients still awaiting surgery had a mean age of 77.2 years (range 48-95 years). Fifty-four were women. Vision had deteriorated by a mean of 0.05 LogMAR units, from Snellen equivalent 6/30 at listing to 6/36, over this time. CONCLUSIONS: Current methods of prioritization for cataract surgery are imperfect, as are the resources for performing adequate levels of cataract surgery. Analysis of a residual waiting list for cataract surgery highlights that the majority (51%) do not ultimately progress to cataract surgery in the public sector for a variety of reasons. During a mean waiting time of 1.5 years vision further deteriorates in this predominantly older population.

The Auckland Cataract Study: demographic, corneal topographic and ocular biometric parameters.

PURPOSE: To determine patient demographics and the ocular biometric parameters in patients presenting for cataract surgery within the public hospital system, in a defined New Zealand population. METHOD: Prospective study of 502 eyes of 488 consecutive patients undergoing cataract surgery. A clinical assessment, including refraction, keratometry (K), A-scan ultrasound and Orbscan II computerized topography was performed on each eye. RESULTS: The mean age of the group was 74.9 +/- 9.8 years (mean +/- SD) with a female predominance (62%). Ethnic origin included 72% European, 8% Maori, 10% Pacific Islander, 4% Asian, 3% Indian and 3% other ethnic origins. The mean Log MAR visual acuity of eyes prior to cataract surgery was 0.88 +/- 0.57 (approximately 6/48(-1)). Corneal topographic (keratometric) maps were classified into five groups: 34% round, 10% oval, 31% symmetrical bow tie, 12% asymmetrical bow tie and 13% irregular. The mean steepest K measurement was 44.1 +/- 1.7 D, the median keratometric astigmatism 0.89 D (range 0.0-6.5 D) and the steepest corneal meridian was horizontal in 50% and vertical in 43%. Seven per cent of corneas were spherical. Refraction revealed a mean sphere of 0.0 +/- 3.1 D and a mean cylinder of -1.2 (range 0.0-7.5 D). Refractive astigmatism was with-the-rule in 15%, against-the-rule in 50% and oblique in 15%, with 20% spherical. Axial length was a mean of 23.14 +/- 1.03 mm. CONCLUSION: Patients presenting for cataract surgery in this study were predominantly elderly, female, of European Caucasian ethnicity and exhibited relatively poor corrected visual acuity in the affected eye. Interestingly, 41% of eyes demonstrated bow-tie topographic patterns, largely exhibiting with-the-rule astigmatism. However, assessment by keratometry or refraction highlighted against-the-rule more frequently; this may have implications for combined cataract and astigmatic surgery. The mean axial length was slightly shorter than expected for a group of predominantly European ethnic origin, although the mean refractive error was emmetropic.

Laser in situ keratomileusis for ametropia after penetrating keratoplasty.

PURPOSE: To evaluate the efficacy of excimer laser in situ keratomileusis (LASIK) in the treatment of refractive errors after penetrating keratoplasty. METHODS: Eight eyes underwent LASIK after a mean 71 months (SD 60) following the initial penetrating keratoplasty. A full ophthalmic assessment was performed before LASIK and at 1 week, 1, 3, 6, and 12 months after surgery. Mean follow-up was 8.6 months (SD 3.2). RESULTS: No eyes lost any Snellen lines of best spectacle-corrected visual acuity at the latest follow-up. Mean reduction in spherical equivalent refraction was 91% from -6.79 D (SD 4.17) to -0.64 D (SD 1.92) and mean reduction of cylinder was 72% from -6.79 D (SD 3.28) to -1.93 D (SD 1.17) at 6 months. Mean surgically induced astigmatism was 5.50 D (SD 2.42) and the index of surgically induced astigmatism divided by the initial cylinder expressed as a percentage was 81%. Mean outcome indices were: correction index 0.87, index of success 0.31, and angle of error 0.95 degrees. Three eyes (43%) achieved a spherical equivalent refraction of +/-0.50 D and 4 eyes (57%) achieved a spherical equivalent refraction of +/-1.00 D of emmetropia. CONCLUSIONS: The efficacy of LASIK after penetrating keratoplasty was good compared to incisional or surface based excimer laser methods and has the advantage of reducing the myopic spherical equivalent refraction in addition to astigmatism, thus improving the uncorrected visual acuities.

Functional, psychological, and satisfaction outcomes of laser in situ keratomileusis for high myopia.

PURPOSE: To identify factors that motivate patients to seek laser in situ keratomileusis (LASIK) treatment for myopia and establish subjective levels of functional improvement and satisfaction across a range of indices after LASIK surgery. SETTING: The Corneal Diseases and Excimer Laser Research Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland. METHODS: In this questionnaire-based, cross-sectional study, an anonymous 34-item questionnaire was forwarded to 50 consecutive patients in a prospective study who had had LASIK for high myopia by a single surgeon at a single center. The questionnaire used visual analog scales, anchored at each end by an adjectival descriptor. The mean preoperative myopia was -10.7 diopters +/- 4.4 (SD). Seventy-six percent of eyes (83% of patients) achieved post-LASIK uncorrected visual acuity (UCVA) of 6/12 or better; 1 eye lost 2 lines of corrected Snellen visual acuity. RESULTS: A 98% reply rate was achieved. The most common motivating factor for pursuing LASIK was to improve UCVA (88%); only 21% rated improved cosmesis as an important motive. Most patients (81% to 100%) reported functional improvement across the spectrum of visual tasks assessed, although 8.8% reported difficulty with nighttime driving. Ninety-six percent felt their UCVA was as good as anticipated, 97.9% were satisfied with the speed of visual improvement, 93.8% achieved the goals for which they had surgery, 97.9% reported an improved quality of life, and 97.9% were satisfied with the overall outcome of LASIK. CONCLUSIONS: Using an anonymous, wide-ranging questionnaire, high levels of functional improvement and satisfaction with the speed of visual recovery and outcome were reported by patients after LASIK for high myopia. Nighttime driving symptoms of variable severity were, however, noted by 8.8% of patients, despite high levels of satisfaction with other aspects of visual function.

Effect of a standard paired arcuate incision and augmentation sutures on postkeratoplasty astigmatism.

To analyze the efficacy of a standardized paired arcuate incision and augmentation suture technique in the treatment of various levels of post-penetrating keratoplasty (PKP) astigmatism. Lions Eye Institute, Royal Perth Hospital, Perth, Australia, and University of Dundee Department of Ophthalmology, Dundee, United Kingdom.A standardized paired arcuate incision and paired augmentation suture technique was used to treat 34 eyes with post-PKP astigmatism ranging from -3.50 to -20.00 diopters (D) at the spectacle plane. The technique consisted of paired arcuate incisions of 3 clock hours, 480 microm deep in the graft-host junction, and 2 pairs of augmentation 10-0 nylon sutures. The mean preoperative cylinder was -9.14 D +/- 4.38 (SD) and the mean postoperative cylinder, -3.59 +/- 1.92 D at the corneal plane after a mean follow-up of 50 +/- 43 weeks. This represents an empirical reduction in mean cylinder of 5. 55 D (60.7%). The Alpins correction index (surgically induced astigmatism [SIA] divided by target induced astigmatism) was calculated for each case, and the mean was 1.01 +/- 0.34, with a median of 0.91. Approximately 53.1% of cases achieved a correction index between 0.80 and 1.20, and the correction index correlated poorly with the initial magnitude of cylinder. A direct numerical relationship between SIA and the initial magnitude of cylinder was observed, although a standard surgical procedure was used in all cases.A simple standardized technique using paired arcuate incisions in the graft-host junction with paired augmentation sutures reduces the amount of cylinder in proportion to the magnitude of the preoperative cylinder and effectively reduces post-PKP astigmatism.