Charles Nj McGhee

Locally administered ocular corticosteroids: benefits and risks.

Corticosteroids, used prudently, are one of the most potent and effective modalities available in the treatment of ocular inflammation. However, they can produce a plethora of adverse ocular and systemic events. In order to optimise and target drug delivery, whilst minimising systemic adverse effects, a diverse range of local ophthalmic preparations and delivery techniques have been developed. Topical drops and ointments remain the primary methods for administration of ocular corticosteroids. However, ocular penetration of topical corticosteroid drops depends upon drug concentration, chemical formulation of corticosteroid, and composition of the vehicle, therefore, apparently small modifications in preparations can produce a more than 20-fold difference in intraocular drug concentration. Periocular injections of corticosteroids continue to have a useful, but limited, therapeutic role and longer acting, intraocular delayed-release devices are in early clinical studies. Although newer corticosteroids with lesser pressure elevating characteristics have been developed, corticosteroid-induced ocular hypertension and glaucoma continue to be significant risks of local and systemic administration. Posterior subcapsular cataract, observed following as little as 4 months topical corticosteroids use, is thought to be due to covalent binding of corticosteroid to lens protein with subsequent oxidation. Inappropriate use of topical corticosteroid in the presence of corneal infections also continues to be a cause of ocular morbidity. Other risks of locally administered ophthalmic corticosteroids include: tear-film instability, epithelial toxicity, crystalline keratopathy, decreased wound strength, orbital fat atrophy, ptosis, limitation of ocular movement, inadvertent intraocular injection, and reduction in endogenous cortisol. This extensive review assesses the therapeutic benefits of locally administered ocular corticosteroids in the context of the risks of adverse effects.

The genetics of keratoconus.

Keratoconus is a relatively common, bilateral, non‐ inflammatory corneal ectasia. The aetiology of this condition is probably multifactorial, or it represents the final common pathway for a variety of different pathological processes. Although a familial history is present only in a minority of cases, one of the major aetiological factors is certainly genetic. This is evidenced by: the conditions familial inheritance; its discordance between monozygotic and dizygotic twins; and its association with other known genetic disorders such as Downs and Marfans syndromes. In the keratoconic cornea, a possible genetic predisposition to increased sensitivity to apoptotic mediators by keratocytes has also been hypothesized. Differences in prevalence between ethnic groups have been identified. Recent advances in computerized topographic diagnostic techniques for keratoconus, including forme fruste keratoconus, enables higher accuracy in delineating abnormal from normal, and helps define study populations for genetic linkage studies. However, genetic heterogeneity and the phenotypic diversity of keratoconus means that genetic analysis continues to be a complex process. None the less, it is foreseeable that over the next decade, improved diagnostic techniques, in combination with molecular genetics, may reveal conclusive data on the precise nature of the genetic inheritance of keratoconus in specific populations. This review considers the evidence that suggests keratoconus is primarily an inherited condition, and examines research strategies aimed at unveiling the genetic predisposition, and the enigma of environmental influences on its phenotypic expression.

Orbscan computerized topography : attributes, applications, and limitations

&NA; An extensive electronic search was undertaken in January 2004 to identify all relevant peer‐reviewed publications on Orbscan slit‐scanning/Placido computerized topography. Ninety‐one publications were identified. These address elevation topography and best‐fit sphere, accuracy and repeatability of anterior and posterior corneal elevation and keratometric maps, comparison of Orbscan‐acquired data and Placido‐based computerized videokeratography instruments, pachymetry measurement and correlation with ultrasound, screening eye‐bank corneas, detection of keratoconus, identifying corneal ectasia after refractive surgery, and miscellaneous applications. Studies were analyzed and critically compared in relation to attributes, applications, and limitations of Orbscan corneal topography. The review highlights advantages of this technique in assessing the cornea in health and disease and after surgery and identifies specific aspects that require further investigation and clarification.

Contemporary in vivo confocal microscopy of the living human cornea using white light and laser scanning techniques: a major review.

In vivo confocal imaging of the cornea has evolved exponentially over the last few decades and it has increasingly emerged from the laboratory to be used in the clinical setting in relation to inherited corneal diseases, corneal infections, contact lens wear and the effects of corneal surgery. This evolution has led to significant enhancement of our knowledge of the living cornea in both its physiological and pathological states. A number of in vivo confocal microscope devices using white, and more recently coherent, light sources have been developed to provide non‐invasive assessment of the corneal microstructure at a lateral resolution of 1–2 µm. The fundamental principles of in vivo confocal microscopy and the key differences between these devices are highlighted in this review. By providing a systematic review of the extensive literature on the human cornea, this perspective paper aims to provide an overview of how in vivo confocal microscopy has contributed to our greater understanding of the human cornea in health, in disease, and following surgery, with a particular emphasis on quantitative data. The utility and limitations of available data are highlighted as are possibilities for the future development of this innovative technology.

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.

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 &mgr;m ± 36.7 [SD]) and Orbscan (566.6 ± 40.7 &mgr;m) pachymetry was statistically significant (P < .001) in the normal eyes; the Orbscan measurement was approximately 28 &mgr;m 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 &mgr;m and 461.9 ± 74.2 &mgr;m, 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 &mgr;m in normal eyes and 150 &mgr;m in post‐LASIK eyes. Conclusion: Central corneal thickness measurements were, on average, 28 &mgr;m higher with the Orbscan than with the ultrasound pachymeter in normal eyes and 13 &mgr;m 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.

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.

Clinical in vivo confocal microscopy of the human cornea in health and disease.

Confocal microscopy enables microstructural analysis of the in vivo cornea, allowing fresh insight into corneal microstructure in health, and in inherited and acquired corneal disease. This method of corneal examination is evolving in an exponential fashion, with rapid advances in technology being mirrored by rapid growth in both research and clinical applications. Whilst initially the evidence base for in vivo confocal microscopy consisted largely of small case studies, in recent years there has been a trend towards collecting quantitative data in an effort to better delineate between heath and disease. Confocal microscopy has been utilised clinically to aid in the diagnosis of infectious keratitis, in particular Acanthamoeba and fungal keratitis, and has also established a role in the diagnosis and phenotyping of corneal dystrophies. This article reviews in vivo confocal microscopy of the human cornea in health and disease and examines clinical and research applications of this new technology.

The Dundee University Scottish Keratoconus study : demographics, corneal signs, associated diseases, and eye rubbing

AimTo investigate and correlate the corneal, refractive, topographic and familial characteristics of a large cohort with keratoconus.MethodsProspective observational study of 200 consecutive patients presenting with keratoconus during the 4 year-period 1997–2000. Subjects were examined at enrolment and at a final review. Data were collected on demographic characteristics, referral route, symptoms, refractive correction, eye rubbing, family history, medical history, slit-lamp biomicroscopic corneal signs, and computerized corneal topography.ResultsMean age at enrolment was 30.9±10.4 (range, 12.2–72) years (N=200, 62.5% male, 93% white Caucasian) with a 5% family history of keratoconus. Atopic diseases included asthma (23%), eczema (14%), and hay fever (30%). Only 9% wore contact lenses before referral. Mean follow-up was 1004 days ±282 (range, 390–1335) and 9.7±8.9 (range, 1.1–60) years from diagnosis. The mean simulated K1 corneal power at enrolment was 51.74±5.36 (range, 42.59–67.32) D and 88.5% exhibited bilateral keratoconus. Fifty-three (15%) topographically confirmed cones exhibited no clinical corneal signs at presentation. At enrollment, 56% had a pachymetry <0.480 mm increasing to 77% at final review. Forty-eight percent of subjects reported significant eye rubbing and there was a highly statistically significant difference (two sample t-test P=0.018) between keratoconus and control groups. TMS-2 axial corneal power was strongly associated with corneal scarring and age at diagnosis. The size of the scarring effect was 2.2 D (95% confidence interval (CI) 1.34, 3.06).ConclusionsThis study provides an overview of a large population with keratoconus highlighting presenting features and clinical and topographic progression over a 4 year-period.

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.