One-year clinical outcomes of a two-step surgical management for keratoconus-topography-guided photorefractive keratectomy/cross-linking after intrastromal corneal ring implantation

PURPOSE - To present the results of same-day topography-guided photorefractive keratectomy (TG-PRK) and corneal collagen cross-linking (CXL) after intrastromal corneal ring (ISCR) implantation in patients with keratoconus. METHODS - Thirty-three patients (41 eyes) aged between 19 and 45 years were included in this prospective study. All patients underwent a femtosecond laser-enabled (Intralase FS; Abbott Medical Optics, Inc.) placement of intracorneal ring segments (Kerarings; Mediphacos, Brazil). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and keratometry readings remained stable for 6 months. Same-day PRK and CXL was subsequently performed in all patients. RESULTS - After 12 months of completion of the procedure, mean UDVA in log of minimal angle of resolution was significantly improved (0.74±0.54-0.10±0.16); CDVA did not improve significantly but 85% of eyes maintained or gained multiple lines of CDVA; mean refraction spherical equivalent improved (from -3.03±1.98 to -0.04±0.99 D), all keratometry readings were significantly reduced, from preoperative values, but coma did not vary significantly from preoperative values. Central corneal thickness and corneal thickness at the thinnest point were significantly (P<0.0001) reduced from 519.76±29.33 and 501.87±31.50 preoperatively to 464.71±36.79 and 436.55±47.42 postoperatively, respectively. Safety and efficacy indices were 0.97 and 0.88, respectively. From 6 months up until more than 1 year of follow-up, further significant improvement was observed only for UDVA (P<0.0001). CONCLUSIONS - Same-day combined TG-PRK and CXL after ISCR implantation is a safe and effective option for improving visual acuity and visual function, and it halts the progression of the keratoconus. The improvements recorded after 6 months of follow-up were maintained or improved upon 1 year after the procedure.

Application of higher-order spectra for automated grading of diabetic maculopathy

Diabetic macular edema (DME) is one of the most common causes of visual loss among diabetes mellitus patients. Early detection and successive treatment may improve the visual acuity. DME is mainly graded into non-clinically significant macular edema (NCSME) and clinically significant macular edema according to the location of hard exudates in the macula region. DME can be identified by manual examination of fundus images. It is laborious and resource intensive. Hence, in this work, automated grading of DME is proposed using higher-order spectra (HOS) of Radon transform projections of the fundus images. We have used third-order cumulants and bispectrum magnitude, in this work, as features, and compared their performance. They can capture subtle changes in the fundus image. Spectral regression discriminant analysis (SRDA) reduces feature dimension, and minimum redundancy maximum relevance method is used to rank the significant SRDA components. Ranked features are fed to various supervised classifiers, viz. Naive Bayes, AdaBoost and support vector machine, to discriminate No DME, NCSME and clinically significant macular edema classes. The performance of our system is evaluated using the publicly available MESSIDOR dataset (300 images) and also verified with a local dataset (300 images). Our results show that HOS cumulants and bispectrum magnitude obtained an average accuracy of 95.56 and 94.39 % for MESSIDOR dataset and 95.93 and 93.33 % for local dataset, respectively.

Cone location and correction of keratoconus with rigid gas-permeable contact lenses

Purpose To evaluate the influence of cone location and corneal cylinder on RGP corrected visual acuities and residual astigmatism in patients with keratoconus. Methods In this prospective study, 156 eyes from 134 patients were enrolled. Complete ophthalmologic examination including manifest refraction, Best spectacle visual acuity (BSCVA), slit-lamp biomicroscopy was performed and corneal topography analysis was done. According to the cone location on the topographic map, the patients were divided into central and paracentral cone groups. Trial RGP lenses were selected based on the flat Sim K readings and a ‘three-point touch’ fitting approach was used. Over contact lens refraction was performed, residual astigmatism (RA) was measured and best-corrected RGP visual acuities (RGPVA) were recorded. Results The mean age (±SD) was 22.1 ± 5.3 years. 76 eyes (48.6%) had central and 80 eyes (51.4%) had paracentral cone. Prior to RGP lenses fitting mean (±SD) subjective refraction spherical equivalent (SRSE), subjective refraction astigmatism (SRAST) and BSCVA (logMAR) were −5.04 ± 2.27 D, −3.51 ± 1.68 D and 0.34 ± 0.14, respectively. There were statistically significant differences between central and paracentral cone groups in mean values of SRSE, SRAST, flat meridian (Sim K1), steep meridian (Sim K2), mean K and corneal cylinder (p-values < 0.05). Comparison of BSCVA to RGPVA shows that vision has improved 0.3 logMAR by RGP lenses (p < 0.0001). Mean (±SD) RA was −0.72 ± 0.39 D. There were no statistically significant differences between RGPVAs and RAs of central and paracentral cone groups (p = 0.22) and (p = 0.42), respectively. Pearson's correlation analysis shows that there is a statistically significant relationship between corneal cylinder and BSCVA and RGPVA, However, the relationship between corneal cylinder and residual astigmatism was not significant. Conclusions Cone location has no effect on the RGP corrected visual acuities and residual astigmatism in patients with keratoconus. Corneal cylinder and Sim K values influence RGP-corrected visual acuities but do not influence residual astigmatism.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

BACKGROUND Tilted disc syndrome (TDS) is associated with characteristic ocular findings. The purpose of this study was to evaluate the ocular, refractive, and biometric characteristics in patients with TDS. METHODS This case-control study included 41 eyes of 25 patients who had established TDS and 40 eyes of 20 healthy control subjects. All participants underwent a complete ocular examination, including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry, keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. RESULTS There were no significant differences in spherical equivalent (P = 0.13) and total astigmatism (P = 0.37) between groups. However, mean best spectacle-corrected visual acuity (Log Mar) was significantly worse in TDS patients (P = 0.003). The lenticular astigmatism was greater in the syndrome group, whereas the corneal component was greater in controls (P = 0.059 and P = 0.028, respectively). The measured biometric features were the same in both groups, except for the lens thickness and lens-axial length factor, which were greater in the TDS group (P = 0.007 and P = 0.055, respectively). CONCLUSIONS Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lenses were characteristic findings in patients with TDS.

The prevalence of anisometropia, amblyopia and strabismus in schoolchildren of Shiraz, Iran

PURPOSE To determine the prevalence of amblyopia, anisometropia, and strabismus in schoolchildren of Shiraz, Iran. MATERIALS AND METHODS A random cluster sampling was used in a cross-sectional study on schoolchildren in Shiraz. Cycloplegic refraction was performed in elementary and middle school children and high school students had non-cylcoplegic refraction. Uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) were recorded for each participant. Anisometropia was defined as spherical equivalent (SE) refraction difference 1.00D or more between two eyes. Amblyopia was distinguished as a reduction of BCVA to 20/30 or less in one eye or 2-line interocular optotype acuity differences in the absence of pathological causes. Cover test was performed for investigating of strabismus. RESULTS Mean age of 2638 schoolchildren was 12.5 years (response rate = 86.06%). Prevalence of anisometropia was 2.31% (95% confidence interval [CI], 1.45 to 3.16). 2.29% of schoolchildren (95% CI, 1.46 to 3.14) were amblyopic. The prevalence of amblyopia in boys and girls was 2.32% and 2.26%, respectively (p = 0.945). Anisometropic amblyopia was found in 58.1% of the amblyopic subjects. The strabismus prevalence was 2.02% (95% CI, 1.18 to 2.85). The prevalence of exotropia and esotropia was 1.30% and 0.59%, respectively. CONCLUSIONS Results of this study showed that the prevalence of anisometropia, amblyopia, and strabismus are in the mid range. The etiology of amblyopia was often refractive, mostly astigmatic, and non-strabismic. Exotropia prevalence increased with age and was the most common strabismus type.

Prevalence of refractive errors among schoolchildren in Shiraz, Iran

PURPOSE To determine the prevalence of refractive errors in Shiraz schoolchildren by age and gender. METHODS For this cross-sectional study, random cluster sampling was carried out from students of the 2008-2009 academic year. After the initial interview, ophthalmic examinations including tests of visual acuity, non-cycloplegic and cycloplegic refraction and binocular vision were performed. Myopia was defined as a spherical equivalent < or =-0.50 dioptre (D), hyperopia as > or =+2.0 D, and astigmatism as a cylinder refraction > or =0.75 D. All values for school grade and gender were directly standardized based on the total student population in the 2008-2009 school year. RESULTS A total of 2130 students were sampled, of which 1872 participated in the study (response rate = 87.88%). The prevalence of uncorrected, best-corrected, presenting and spectacle corrected visual acuity of 6/12 or worse in the better eye was 6.46%, 0%, 1.49% and 0.9%, respectively. The prevalence rates of myopia, hyperopia and astigmatism were 4.35% (95% confidence interval [CI]: 2.89-5.82%), 5.04% (95% CI: 3.50-6.58%), and 11.27% (95% CI: 9.81-12.74%), respectively. Anisometropia was detected in 2.58% of schoolchildren. The prevalence of hyperopia significantly decreased with age (P = 0.021). CONCLUSIONS Compared with other reported rates, the prevalence of myopia in the schoolchildren of Shiraz is similar to that in most places excluding East Asian countries, and that of hyperopia is in the mid range.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

Purpose: To evaluate the ocular refractive and biometric characteristics in patients with tilted disc syndrome (TDS). Methods: This case-control study comprised 41 eyes of 25 patients with established TDS and forty eyes of 20 age- and sex-matched healthy control subjects. All had a complete ocular examination including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. Results: There were no significant differences in spherical equivalent (p = 0.334) and total astigmatism (p= 0.246) between groups. However, mean best spectacular corrected visual acuity was significantly worse in TDS patients (P < 0.001). The lenticular astigmatism was significantly greater in the syndrome group, while the corneal component was greater in the controls (p = 0.004 and p = 0.002, respectively). The measured biometric features were the same in both groups, except for the lens thickness, relative lens position, and lens-axial length factor which were greater in the TDS group (p = 0.002, p = 0.015, and p = 0.025, respectively). Conclusions: Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lens were characteristic findings in patients with TDS.

Persistent anterior chamber silicone oil and myopia

A 60-year-old male experienced a marked unilateral myopic shift of 20 D following attempted removal of intravitreal heavy silicone oil (HSO) used in the treatment of inferior proliferative vitreous retinopathy following retinal detachment. Examination revealed HSO adherent to the corneal endothelium forming a convex interface with the aqueous, obscuring the entire pupil, which required surgical intervention to restore visual acuity. This case highlights the potential ocular complications associated with silicone oil migration into the anterior chamber, which include corneal endothelial decompensation and a significant increase in myopia.

Association between glaucoma and at–fault motor vehicle collision involvement among older drivers

Objective To examine the association between glaucoma and motor vehicle collision (MVC) involvement among older drivers, including the role of visual field impairment that may underlie any association found. Design A retrospective population-based study Participants A sample of 2,000 licensed drivers aged 70 years and older who reside in north central Alabama. Methods At-fault MVC involvement for five years prior to enrollment was obtained from state records. Three aspects of visual function were measured: habitual binocular distance visual acuity, binocular contrast sensitivity and the binocular driving visual field constructed from combining the monocular visual fields of each eye. Poisson regression was used to calculate crude and adjusted rate ratios (RR) and 95% confidence intervals (CI). Main Outcomes Measures At-fault MVC involvement for five years prior to enrollment. Results Drivers with glaucoma (n = 206) had a 1.65 (95% confidence interval [CI] 1.20-2.28, p = 0.002) times higher MVC rate compared to those without glaucoma after adjusting for age, gender and mental status. Among those with glaucoma, drivers with severe visual field loss had higher MVC rates (RR = 2.11, 95% CI 1.09-4.09, p = 0.027), whereas no significant association was found among those with impaired visual acuity and contrast sensitivity. When the visual field was sub-divided into six regions (upper, lower, left, and right visual fields; horizontal and vertical meridians), we found that impairment in the left, upper or lower visual field was associated with higher MVC rates, and an impaired left visual field showed the highest RR (RR = 3.16, p = 0.001) compared to other regions. However, no significant association was found in deficits in the right side or along the horizontal or vertical meridian. Conclusions A population-based study suggests that older drivers with glaucoma are more likely to have a history of at-fault MVC involvement than those without glaucoma. Impairment in the driving visual field in drivers with glaucoma appears to have an independent association with at-fault MVC involvement, whereas visual acuity and contrast sensitivity impairments do not.

Standardised antibacterial Manuka honey in the management of persistent post-operative corneal oedema: A case series

Background Corneal oedema is a common post-operative problem that delays or prevents visual recovery from ocular surgery. Honey is a supersaturated solution of sugars with an acidic pH, high osmolarity and low water content. These characteristics inhibit the growth of micro-organisms, reduce oedema and promote epithelialisation. This clinical case series describes the use of a regulatory approved Leptospermum species honey ophthalmic product, in the management of post-operative corneal oedema and bullous keratopathy. Methods A retrospective review of 18 consecutive cases (30 eyes) with corneal oedema persisting beyond one month after single or multiple ocular surgical procedures (phacoemulsification cataract surgery and additional procedures) treated with Optimel Antibacterial Manuka Eye Drops twice to three times daily as an adjunctive therapy to conventional topical management with corticosteroid, aqueous suppressants, hypertonic sodium chloride five per cent, eyelid hygiene and artificial tears. Visual acuity and central corneal thickness were measured before and at the conclusion of Optimel treatment. Results A temporary reduction in corneal epithelial oedema lasting up to several hours was observed after the initial Optimel instillation and was associated with a reduction in central corneal thickness, resolution of epithelial microcysts, collapse of epithelial bullae, improved corneal clarity, improved visualisation of the intraocular structures and improved visual acuity. Additionally, with chronic use, reduction in punctate epitheliopathy, reduction in central corneal thickness and improvement in visual acuity were achieved. Temporary stinging after Optimel instillation was experienced. No adverse infectious or inflammatory events occurred during treatment with Optimel. Conclusions Optimel was a safe and effective adjunctive therapeutic strategy in the management of persistent post-operative corneal oedema and warrants further investigation in clinical trials.

Sampling accuracy of reef resource inventory technique

A new technique called the reef resource inventory (RRI) was developed to map the distribution and abundance of benthos and substratum on reefs. The rapid field sampling technique uses divers to visually estimate the percentage cover of categories of benthos and substratum along 2x20 in plotless strip-transects positioned randomly over the tops, and systematically along the edge of reefs. The purpose of this study was to compare the relative sampling accuracy of the RRI against the line intercept transect technique (LIT), an international standard for sampling reef benthos and substratum. Analysis of paired sampling with LIT and RRI at 51 sites indicated sampling accuracy was not different (P > 0.05) for 8 of the 12 benthos and substratum categories used in the study. Significant differences were attributed to small-scale patchiness and cryptic coloration of some benthos; effects associated with sampling a sparsely distributed animal along a line versus an area; difficulties in discriminating some of the benthos and substratum categories; and differences due to visual acuity since LIT measurements were taken by divers close to the seabed whereas RRI measurements were taken by divers higher in the water column. The relative cost efficiency of the RRI technique was at least three times that of LIT for all benthos and substratum categories and as much as 10 times higher for two categories. These results suggest that the RRI can be used to obtain reliable and accurate estimates of relative abundance of broad categories of reef benthos and substratum.

Changes in straylight and corneal light scattering in a newly diagnosed case of type 2 diabetes

Visual problems may be the first symptoms of diabetes. There have been several reports of transient changes in refraction of people newly diagnosed with diabetes. Visual acuity and refraction may be affected when there are ocular biometric changes. Small but significant biometrical changes have been found by some authors during hyperglycaemia and during reduction of hyperglycaemia.[4] Here, we describe a case of type 2 diabetes that was detected from ocular straylight and intraocular thickness measurements...

Zeaxanthin biofortification of sweet-corn and factors affecting zeaxanthin accumulation and colour change

Zeaxanthin, along with its isomer lutein, are the major carotenoids contributing to the characteristic colour of yellow sweet-corn. From a human health perspective, these two carotenoids are also specifically accumulated in the human macula, and are thought to protect the photoreceptor cells of the eye from blue light oxidative damage and to improve visual acuity. As humans cannot synthesise these compounds, they must be accumulated from dietary components containing zeaxanthin and lutein. In comparison to most dietary sources, yellow sweet-corn (Zea mays var. rugosa) is a particularly good source of zeaxanthin, although the concentration of zeaxanthin is still fairly low in comparison to what is considered a supplementary dose to improve macular pigment concentration (2 mg/person/day). In our present project, we have increased zeaxanthin concentration in sweet-corn kernels from 0.2 to 0.3 mg/100 g FW to greater than 2.0 mg/100 g FW at sweet-corn eating-stage, substantially reducing the amount of corn required to provide the same dosage of zeaxanthin. This was achieved by altering the carotenoid synthesis pathway to more than double total carotenoid synthesis and to redirect carotenoid synthesis towards the beta-arm of the pathway where zeaxanthin is synthesised. This resulted in a proportional increase of zeaxanthin from 22% to 70% of the total carotenoid present. As kernels increase in physiological maturity, carotenoid concentration also significantly increases, mainly due to increased synthesis but also due to a decline in moisture content of the kernels. When fully mature, dried kernels can reach zeaxanthin and carotene concentrations of 8.7 mg/100 g and 2.6 mg/100 g, respectively. Although kernels continue to increase in zeaxanthin when harvested past their normal harvest maturity stage, the texture of these 'over-mature' kernels is tough, making them less appealing for fresh consumption. Increase in zeaxanthin concentration and other orange carotenoids such as p-carotene also results in a decline in kernel hue angle of fresh sweet-corn from approximately 90 (yellow) to as low as 75 (orange-yellow). This enables high-zeaxanthin sweet-corn to be visually-distinguishable from standard yellow sweet-corn, which is predominantly pigmented by lutein.

Molecular genetics of X-linked cone-rod dystrophy and Åland Island eye disease

Inherited retinal diseases are the most common cause of vision loss among the working population in Western countries. It is estimated that ~1 of the people worldwide suffer from vision loss due to inherited retinal diseases. The severity of these diseases varies from partial vision loss to total blindness, and at the moment no effective cure exists. To date, nearly 200 mapped loci, including 140 cloned genes for inherited retinal diseases have been identified. By a rough estimation 50% of the retinal dystrophy genes still await discovery. In this thesis we aimed to study the genetic background of two inherited retinal diseases, X-linked cone-rod dystrophy and Åland Island eye disease. X-linked cone-rod dystrophy (CORDX) is characterized by progressive loss of visual function in school age or early adulthood. Affected males show reduced visual acuity, photophobia, myopia, color vision defects, central scotomas, and variable changes in fundus. The disease is genetically heterogeneous and two disease loci, CORDX1 and CORDX2, were known prior to the present thesis work. CORDX1, located on Xp21.1-11.4, is caused by mutations in the RPGR gene. CORDX2 is located on Xq27-28 but the causative gene is still unknown. Åland Island eye disease (AIED), originally described in a family living in Åland Islands, is a congenital retinal disease characterized by decreased visual acuity, fundus hypopigmentation, nystagmus, astigmatism, red color vision defect, myopia, and defective night vision. AIED shares similarities with another retinal disease, congenital stationary night blindness (CSNB2). Mutations in the L-type calcium channel α1F-subunit gene, CACNA1F, are known to cause CSNB2, as well as AIED-like disease. The disease locus of the original AIED family maps to the same genetic interval as the CACNA1F gene, but efforts to reveal CACNA1F mutations in patients of the original AIED family have been unsuccessful. The specific aims of this study were to map the disease gene in a large Finnish family with X-linked cone-rod dystrophy and to identify the disease-causing genes in the patients of the Finnish cone-rod dystrophy family and the original AIED family. With the help of linkage and haplotype analyses, we could localize the disease gene of the Finnish cone-rod dystrophy family to the Xp11.4-Xq13.1 region, and thus establish a new genetic X-linked cone-rod dystrophy locus, CORDX3. Mutation analyses of candidate genes revealed three novel CACNA1F gene mutations: IVS28-1 GCGTC>TGG in CORDX3 patients, a 425 bp deletion, comprising exon 30 and flanking intronic regions in AIED patients, and IVS16+2T>C in an additional Finnish patient with a CSNB2-like phenotype. All three novel mutations altered splice sites of the CACNA1F gene, and resulted in defective pre-mRNA splicing suggesting altered or absent channel function as a disease mechanism. The analyses of CACNA1F mRNA also revealed novel alternative wt splice variants, which may enhance channel diversity or regulate the overall expression level of the channel. The results of our studies may be utilized in genetic counseling of the families, and they provide a basis for studies on the pathogenesis of these diseases. In the future, the knowledge of the genetic defects may be used in the identification of specific therapies for the patients.

Corneal recovery after uncomplicated and complicated PRK and LASIK

Refractive errors, especially myopia, seem to increase worldwide. Concurrently, the number of surgical refractive corrections has increased rapidly, with several million procedures performed annually. However, excimer laser surgery was introduced after a limited number of studies done with animals and to date there still are only few long-term follow-up studies of the results. The present thesis aims to evaluate the safety and functional outcome of, as well as to quantify the cellular changes and remodelling in the human cornea after, photorefractive keratectomy (PRK) and laser assisted in situ keratomileusis (LASIK). These procedures are the two most common laser surgical refractive methods. In Study I, myopic ophthalmic residents at Helsinki University Eye Hospital underwent a refractive correction by PRK. Five patients were followed up for 6 months to assess their subjective experience in hospital work and their performance in car driving simulator and in other visuomotor functions. Corneal morphological changes were assessed by in vivo confocal microscopy (ivCM). Study II comprised 14 patients who had undergone a PRK operation in 1993-1994. Visual acuity was examined and ivCM examinations performed 5 years postoperatively. In Study III 15 patients received LASIK refractive correction for moderate to high myopia (-6 - -12 D). Their corneal recovery was followed by ivCM for 2 years. Diffuse lamellar keratitis (DLK) is a common but variable complication of LASIK. Yet, its aetiology remains unknown. In Study IV we examined six patients who had developed DLK as a consequence of formation of an intraoperative or post-LASIK epithelial defect, to assess the corneal and conjunctival inflammatory reaction. In the whole series, the mean refractive correction was -6.46 diopters. The best spectacle corrected visual acuity (BSCVA) improved in 30 % of patients, whereas in four patients BSCVA decreased slightly. The mean achieved refraction was 0.35 D undercorrected. After PRK, the stromal scar formation was highest at 2 to 3 months postoperatively and subsequently decreased. At 5 years increased reflectivity in the subepithelial stroma was observed in all patients. Interestingly, no Bowman s layer was detected in any patient. Subbasal nerve fiber bundle(snfb) regeneration could be observed already at 2 months in 2 patients after PRK. After 5 years, all corneas presented with snfb, the density of which, however, was still lower than in control corneas. LASIK induced a hypocellular area on both sides of the flap interface. A decrease of the most anterior keratocyte density was also observed. In the corneas that developed DLK, inflammatory cell-type objects were present in the flap interface in half of the patients. The other patients presented only with keratocyte activation and highly reflective extracellular matrix. These changes resolved completely with medication and time. Snfb regeneration was first detected at one month post-LASIK, but still after two years the density of snfb, however, was only 64 % of the preoperative values. The performance of ophthalmological examinations and microsurgery without spectacles was easier postoperatively, which was appreciated by the residents. Both PRK and LASIK showed moderate to good accuracy and high safety. In terms of visual perception and subjective evaluation, few patients stated any complaints in the whole series of studies. Instead, the majority of patients experienced a marked improvement in everyday life and work performance. PRK and LASIK have shown similar results, with good long term morphological healing. It seems evident that, even without the benefit of over-20-year follow-up results, these procedures are sufficiently safe and accurate for refractive corrections and corneal reshaping.