Biocompatibility, SiH lenses and the impact of hydration on comfort

Silicone hydrogel (SiH) contact lenses have been available for over a decade. During that time, these highly innovative materials and designs have continually improved and now represent a major percentage of fits within the global contact lens market.1 Their high oxygen transmissibility has drastically reduced the incidence of hypoxia-related conditions such as corneal edema, limbal hyperaemia, and corneal vascularisation.2,3 However, there remain significant challenges in the quest for the ideal contact lens. The silicone material used in SiH contact lenses is inherently more hydrophobic than the non-silicone hydrogel materials. SiH lens manufacturers must find ways to overcome lens surface hydrophobicity since it can create issues in terms of lens wettability and surface deposition. Achieving ideal lens water content presents yet another challenge since increasing water content in a silicone hydrogel lens can reduce oxygen transmissibility. This is because increasing water content results in decreased silicone content in the lens and silicone is a better transmitter of oxygen than water.

Langerhans cells in the cornea of diabetic patients : relevance to diabetic neuropathy

Purpose The presence of a lymphocytic infiltration in autonomic ganglia and an increased prevalence of autoantibodies and iritis in diabetic patients with autonomic neuropathy suggests a role for autoimmune mechanisms in the development of diabetic and perhaps somatic neuropathy. Corneal Langerhans cells are antigenpresenting cells which can be identified in corneal immunologic conditions using in-vivo confocal microscopy. The aim of this study was to assess the presence and density of Langerhans cells (LCs) in Bowman’s layer of the cornea in diabetic patients with varying degrees of neuropathy compared to healthy control subjects. Method 128 diabetic patients aged 58±1 years with differing severity of neuropathy (NDS – 4.7±0.28) and 26 control subjects aged 53±3 years were examined with in-vivo corneal confocal microscopy to quantify the density of “Langerhans cells” (LCs). Results LCs were observed more often in diabetic patients (73.8%) compared to control subjects (46.1%), P = 0.001. The LC density (number/mm2) was also significantly increased in diabetic patients (17.73±1.45) compared to control subjects (6.94±1.58, P = 0.001). There was a significant correlation between the density of LCs with age (r = 0.162, P = 0.047) and severity of neuropathy assessed by NDS (r =−0.202, P = 0.02). Conclusions In vivo corneal confocal microscopy enables quantification of Langerhans cells in Bowman’s layer of the cornea. There is a relationship between density of LCs and the degree of nerve damage. Corneal confocal microscopy could be a valuable tool to establish the role of immune mediated corneal nerve damage and provide insights into the pathogenesis of diabetic neuropathy.

Repeatability of confocal microscopy measurements on the central and peripheral cornea

Purpose To assess confocal microscopy repeatability (ConfoScan3, Nidek, Italy) when assessing the morphology of the limbus, midperipheral and central cornea. Method The central, mid-peripheral and limbal cornea (temporal and nasal) of the right eye of 8 subjects were examined with a ConfoScan3 in two different visits, at least six months apart. Bland-Altman repeatability was measured for 29 parameters: basal cell density and size, anterior and posterior keratocyte densities (AKD/PKD), endothelial cell density, polymegethism, pleomorphism, mean area and sides of endothelial cells - in the five different corneal areas examined. Results As a percentage of the mean absolute values, repeatability of 0–10% was classified as “excellent”, between 10–30% as “acceptable” and over 30% as “poor”. Repeatability was excellent for 14% of parameters and acceptable for 52% of parameters. The number of endothelial cell sides in the central cornea demonstrated the best repeatability (2.0%) whilst mid-temporal PKD showed the poorest repeatability (53.7%). Conclusions Confocal microscopy is at least an adequately repeatablemethodof evaluating the various corneal layers at different locations. Our dataset supports the ongoing use of the technique in research and clinical practice.

The role of RGPs in modern practice

Has the 1998 prediction of a well-known contact lens researcher – that rigid contact lenses will be obsolete by the year 2010 – come to fruition? This Eulogy to RGPs will demonstrate why it has. A recent survey of international contact lens prescribing trends shows that rigid lenses constituted less than 5% of all contact lenses prescribed in 16 out of 27 nations surveyed. This compares with rigid lenses representing 100% of all lenses prescribed 1965 and about 40% in 1990). With the wide range of sophisticated soft lens materials available today, including super-permeable silicone hydrogels, and designs capable of correcting astigmatism and presbyopia, there is now no need to fit cosmetic patients with rigid lenses, with the associated intractable problems of rigid lens-induced ptosis, 3 and 9 o’clock, staining, lens binding, corneal warpage and adaptation discomfort. Orthokeratology is largely a fringe application of marginal efficacy, and the notion that rigid lenses arrest myopia progression is flawed. That last bastion of rigid lens practice – fitting patients with severely distorted corneas as in keratoconus – is about to crumble in view of a number of demonstrations by independent research groups of the efficacy of custom-designed wavefront-corrected soft contact lenses for the correction of keratoconus. It is concluded that rigid contact lenses now have no place in modern contact lens practice.

Comparing skin biopsy with confocal microscopy : diagnostic yield of nerve fiber density

Background and aims: The assessment of intra-epidermal nerve fiber density (IENFD) in skin biopsies and corneal nerve fiber density (CNFD) using corneal confocal microscopy (CCM) provides promising techniques to detect small nerve fiber damage in patients with peripheral neuropathy. To help define the clinical utility of each of these techniques in patients with diabetic neuropathy we have assessed sensitivity and specificity of IENFD and CNFD in predicting the following: 1) diabetic polyneuropathy (DPN); 2) risk of foot ulceration (RFU); 3) initial small fiber neuropathy (iSFN); 4) severe small fiber neuropathy (sSFN)...

Oxygen; my view

Oxygen has been the “holy grail” of contact lens wear for over 100 years, but it is just one piece of a complex jigsaw puzzle. Clearly, high oxygen transmissibility (Dk/t) silicone hydrogel lenses meet the oxygen needs of the cornea. The Dk/t of these lenses is over 75 Dk units, which is far above that of the “best” hydrogel lenses (30 Dk units). Clinical trials have failed to reveal any hypoxic problemswith silicone hydrogel lenses. Thus, conditions such as epithelial microcysts, limbal redness, hypoxic staining, stromal neovascularisation, oedema and endothelial polymegethism do not occur with these lenses. My view is that – looking at the “big picture” – we are far better off now that we have silicone hydrogel lenses.

Longitudinal assessment of neuropathy in diabetes using novel ophthalmic markers (LANDMark) : baseline findings

Purpose Over the past decade, corneal nerve morphology and corneal sensation threshold have been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of a Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic Markers (LANDMark). Methods The LANDMark Study is a 5-year, two-site, natural history (observational) study of individuals with Type 1 diabetes stratified into those with (T1W) and without (T1WO) neuropathy according to the Toronto criteria, and control subjects. All study participants undergo detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal esthesiometry. Results 396 eligible individuals (208 in Brisbane and 188 in Manchester) were assessed: 76 T1W, 166 T1WO and 154 controls. Corneal sensation threshold (mbars) was significantly higher in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (P=0.002); post-hoc analysis (PHA) revealed no difference between T1WO and controls (Tukey HSD, P=0.502). Corneal nerve fiber length (mm/mm2) (CNFL) was lower in T1W (13.8 ± 6.4) than T1WO (19.1 ± 5.8) and controls (23.2 ± 6.3) (P<0.001); PHA revealed CNFL to be lower in T1W than T1WO, and lower in both of these groups than controls (P<0.001). Corneal nerve branch density (branches/mm2) (CNBD) was significantly lower in T1W (40 ± 32) than T1WO (62 ± 37) and controls (83 ± 46) (P<0.001); PHA showed CNBD was lower in T1W than T1WO, and lower in both groups than controls (P<0.001). Alcohol and cigarette consumption did not differ between groups, although age, BMI, BP, waist circumference, HbA1c, albumin-creatinine ratio, and cholesterol were slightly greater in T1W than T1WO (p<0.05). Some site differences were observed. Conclusions The LANDMark baseline findings confirm that corneal sensitivity and corneal nerve morphometry can detect differences in neuropathy status in individuals with Type 1 diabetes and healthy controls. Corneal nerve morphology is significantly abnormal even in diabetic patients ‘without neuropathy’ compared to control participants. Results of the longitudinal trial will assess the capability of these tests for monitoring change in these parameters over time as potential surrogate markers for neuropathy.

Development of Contact Lenses from a Biomaterial Point of View – Materials, Manufacture, and Clinical Application

Rigid lenses, which were originally made from glass (between 1888 and 1940) and later from polymethyl methacrylate or silicone acrylate materials, are uncomfortable to wear and are now seldom fitted to new patients. Contact lenses became a popular mode of ophthalmic refractive error correction following the discovery of the first hydrogel material – hydroxyethyl methacrylate – by Czech chemist Otto Wichterle in 1960. To satisfy the requirements for ocular biocompatibility, contact lenses must be transparent and optically stable (for clear vision), have a low elastic modulus (for good comfort), have a hydrophilic surface (for good wettability), and be permeable to certain metabolites, especially oxygen, to allow for normal corneal metabolism and respiration during lens wear. A major breakthrough in respect of the last of these requirements was the development of silicone hydrogel soft lenses in 1999 and techniques for making the surface hydrophilic. The vast majority of contact lenses distributed worldwide are mass-produced using cast molding, although spin casting is also used. These advanced mass-production techniques have facilitated the frequent disposal of contact lenses, leading to improvements in ocular health and fewer complications. More than one-third of all soft contact lenses sold today are designed to be discarded daily (i.e., ‘daily disposable’ lenses).

Nanohybrids of silver particles on clay platelets delaminate Pseudomonas biofilms

Aim To evaluate the effectiveness of novel nanohybrids, composed of silver nanoparticles and nanoscale silicate platelets, to clear Pseudomonas aeruginosa biofilms. Materials & methods The nanohybrids were manufactured from an in situ reduction of silver salts in the silicate platelet dispersion, and then applied to biofilms in vitro and in vivo. Results In reference to the biocidal effects of gentamycin, the nanohybrids mitigated the spreading of the biofilms, and initiated robust cell death and exfoliation from the superficial layers of the biofilms in vitro. In vivo, the nanohybrids exhibited significant therapeutic effects by eliminating established biofilms from infected corneas and promoting the recovery of corneal integrity. Conclusion All of the evaluations indicate the high potency of the newly developed silver nanoparticle/nanoscale silicate platelet nanohybrids for eliminating biofilms.

New technologies for assessing the contact lens wearing eye

New technologies for examination of the anterior eye in contact lens practice don’t appear to have taken a huge leap in the past decade however there a several novel adaptations of existing technology worthy of note. In other areas of health we have self-diagnosis via smartphone or other gadgets adapted as medical devices. In practice and research in vitro and in vivo new adaptive technologies have expanded our capabilities in assessing the anterior eye, in particular corneal and conjunctival confocal microscopy.

Changes in ocular biometrics and refraction during near work in downward gaze over time

PURPOSE To investigate changes in the characteristics of the corneal optics, total optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 min. METHODS Ten emmetropes (mean - 0.14 ± 0.24 DS) and 10 myopes (mean - 2.26 ± 1.42 DS) aged from 18 to 30 years were recruited. To measure ocular biometrics and corneal topography in downward gaze, an optical biometer (Lenstar LS900) and a rotating Scheimpflug camera (Pentacam HR) were inclined on a custom built, height and tilt adjustable table. The total optics of the eye were measured in downward gaze with binocular fixation using a modified Shack-Hartmann wavefront sensor. Initially, subjects performed a distance viewing task at primary gaze for 10 min to provide a "wash-out" period for prior visual tasks. A distance task (watching video at 6 m) in downward gaze (25°) and a near task (watching video on a portable LCD screen with 2.5 D accommodation demand) in primary gaze and 25°downward gaze were then carried out, each for 10 min in a randomized order. During measurements, in dichoptic view, a Maltese cross was fixated with the right (untested) eye and the instrument’s fixation target was fixated with the subject’s tested left eye. Immediately after (0 min), 5 and 10 min from the commencement of each trial, measurements of ocular parameters were acquired in downward gaze. RESULTS Axial length exhibited a significant increase with downward gaze and accommodation over time (p<0.05). The greatest axial elongation was observed in downward gaze with 2.5 D accommodation after 10 min (mean change from baseline 23±3 µm). Downward gaze also caused greater changes in anterior chamber depth (ACD) and lens thickness (LT) with accommodation (ACD mean change -163±12µm at 10 min; LT mean change 173±17 µm at 10 min) compared to primary gaze with accommodation (ACD mean change -138±12µm at 10 min; LT mean change 131±15 µm at 10 min). Both corneal power and total ocular power changed by a small but significant amount with downward gaze (p<0.05), resulting in a myopic shift (~0.10 D) in the spherical power of the eye compared with primary gaze. CONCLUSION The axial length, anterior biometrics and ocular refraction change significantly with accommodation in downward gaze as a function of time. These findings provide new insights into the optical and bio-mechanical changes of the eye during typical near tasks.

Myopic anisometropia : ocular characteristics and aetiological considerations

Anisometropia represents a unique example of ocular development, where the two eyes of an individual, with an identical genetic background and seemingly subject to identical environmental influences, can grow asymmetrically to produce significantly different refractive errors. This review provides an overview of the research examining myopic anisometropia, the ocular characteristics underlying the condition and the potential aetiological factors involved. Various mechanical factors are discussed, including corneal structure, intraocular pressure and forces generated during near work that may contribute to development of anisomyopia. Potential visually guided mechanisms of unequal ocular growth are also explored, including the influence of astigmatism, accommodation, higher-order aberrations and the choroidal response to altered visual experience. The association between binocular vision, ocular dominance and asymmetric refraction is also considered, along with a review of the genetic contribution to the aetiology of myopic anisometropia. Despite a significant amount of research into the biomechanical, structural and optical characteristics of anisometropic eyes, there is still no unifying theory, which adequately explains how two eyes within the same visual system grow to different endpoints.

Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic MARKers (LANDMark): Baseline findings

Purpose:Over the past decade, corneal nerve morphology and corneal sensation threshold have been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of a Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic Markers (LANDMark). Methods:The LANDMark Study is a 5-year, two-site, natural history (observational) study of individuals with Type 1 diabetes stratified into those with (T1W) and without (T1WO) neuropathy according to the Toronto criteria, and control subjects. All study participants undergo detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal esthesiometry. Results:396 eligible individuals (208 in Brisbane and 188 in Manchester) were assessed: 76 T1W, 166 T1WO and 154 controls. Corneal sensation threshold (mbars) was significantly higher in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (P=0.002); post-hoc analysis (PHA) revealed no difference between T1WO and controls (Tukey HSD, P=0.502). Corneal nerve fiber length (mm/mm2) (CNFL) was lower in T1W (13.8 ± 6.4) than T1WO (19.1 ± 5.8) and controls (23.2 ± 6.3) (P<0.001); PHA revealed CNFL to be lower in T1W than T1WO, and lower in both of these groups than controls (P<0.001). Corneal nerve branch density (branches/mm2) (CNBD) was significantly lower in T1W (40 ± 32) than T1WO (62 ± 37) and controls (83 ± 46) (P<0.001); PHA showed CNBD was lower in T1W than T1WO, and lower in both groups than controls (P<0.001). Alcohol and cigarette consumption did not differ between groups, although age, BMI, BP, waist circumference, HbA1c, albumin-creatinine ratio, and cholesterol were slightly greater in T1W than T1WO (p<0.05). Some site differences were observed. Conclusions:The LANDMark baseline findings confirm that corneal sensitivity and corneal nerve morphometry can detect differences in neuropathy status in individuals with Type 1 diabetes and healthy controls. Corneal nerve morphology is significantly abnormal even in diabetic patients ‘without neuropathy’ compared to control participants. Results of the longitudinal trial will assess the capability of these tests for monitoring change in these parameters over time as potential surrogate markers for neuropathy.

Late reactivation of herpes zoster keratitis results in band keratopathy

Purpose To report an unusual case of a late-stage reactivation of immune stromal keratitis associated with herpes zoster ophthalmicus (HZO), occurring without any apparent predisposing factors, more than 4 years after an acute zoster dermatomal rash. Significant corneal hypoesthesia and a central band keratopathy developed within 6 months of the late-stage reactivation. The clinical case management, issues associated with management, and management options are discussed, including the use of standardized, regulatory approved, antibacterial medical honey. Case Report An 83-year-old woman presented for routine review with a reactivation of right anterior stromal keratitis and mild anterior uveitis, occurring more than 4 years after an acute HZO dermatomal rash and an associated initial episode of anterior stromal keratitis. Corneal sensation became markedly impaired, and over the subsequent 6 months, a right central band keratopathy developed despite oral antiviral and topical steroid therapy. Visual acuity with pinhole was reduced to 20/100 in the affected eye and moderate irritation and epiphora were experienced. The patient declined the surgical intervention options of chelation, lamellar keratectomy, and phototherapeutic keratectomy to treat the band keratopathy. Longer-term management has involved preservative-free artificial tears, eyelid hygiene, standardized antibacterial medical honey, topical nonpreserved steroid, and UV-protective wraparound sunglasses. The clinical condition has improved over 14 months with this ocular surface management regimen, and visual acuity of 20/30 is currently achieved in a comfortable eye. Conclusions The chronic and recurrent nature of HZO can be associated with significant corneal morbidity, even many years after the initial zoster episode. Long-term review and management of patients with a history of herpes zoster stromal keratitis are indicated following the initial corneal involvement. Standardized antibacterial medical honey can be considered in the management of the chronic ocular surface disease associated with HZO and warrants further evaluation in clinical trials.