Correlation between corneal and scleral thickness in glaucoma

PURPOSE: To assess the correlation between central corneal thickness (CCT) and anterior scleral thickness (ST) in patients of primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and ocular hypertension (OHT). PATIENTS AND METHODS: Consecutive patients with OHT, POAG, NTG, and normal individuals were recruited. CCT was measured by ultrasonic pachymetry, whereas ST was measured using ultrasonic biomicroscopy at the temporal quadrant, 2'mm posterior to the scleral spur. Investigators were masked to the diagnosis and CCT/ ultrasonic biomicroscopy data. Correlation between mean CCT and ST was analyzed. RESULTS: One hundred and twenty-four subjects (31 with OHT, 31 with POAG, 31 with NTG, and 31 normal individuals) were enrolled. The CCT (OHT 548.06±30.45'µm; POAG 519.39±42.95'µm; NTG 505.81±27.23'µm; controls 529.90±43.40'µm) was found to be thicker in patients with OHT than POAG (P=0.004) or NTG (P

Measurement of scleral thickness in humans using anterior segment optical coherent tomography

Anterior segment optical coherent tomography (AS-OCT, Visante; Zeiss) is used to examine meridional variation in anterior scleral thickness (AST) and its association with refractive error, ethnicity and gender. Scleral cross-sections of 74 individuals (28 males; 46 females; aged between 18-40 years (27.7±5.3)) were sampled twice in random order in 8 meridians: [superior (S), inferior (I), nasal (N), temporal (T), superior-temporal (ST), superior-nasal (SN), inferior-temporal (IT) and inferior-nasal (IN)]. AST was measured in 1mm anterior-toposterior increments (designated the A-P distance) from the scleral spur (SS) over a 6mm distance. Axial length and refractive error were measured with a Zeiss IOLMaster biometer and an open-view binocular Shin-Nippon autorefractor. Intra- And inter-observer variability of AST was assessed for each of the 8 meridians. Mixed repeated measures ANOVAs tested meridional and A-P distance differences in AST with refractive error, gender and ethnicity. Only right eye data were analysed. AST (mean±SD) across all meridians and A-P distances was 725±46μm. Meridian SN was the thinnest (662±57μm) and I the thickest (806 ±60μm). Significant differences were found between all meridians (p<0.001), except S:ST, IT:IN, IT:N and IN:N. Significant differences between A-P distances were found except between SS and 6 mm and between 2 and 4mm. AST measurements at 1mm (682±48 μm) were the thinnest and at 6mm (818±49 μm) the thickest (p<0.001); a significant interaction occurred between meridians and A-P distances (p<0.001). AST was significantly greater (p<0.001) in male subjects but no significant differences were found between refractive error or ethnicity. Significant variations in AST occur with regard to meridian and distance from the SS and may have utility in selecting optimum sites for pharmaceutical or surgical intervention.

Evaluation of scleral and corneal thickness in keratoconus patients

PURPOSE To determine whether the scleral stroma is affected as much as the corneal stroma in keratoconus. SETTING University Eye Clinic, Bern, Switzerland. DESIGN Comparative case-control study. METHODS Eyes with keratoconus (keratoconus group) and eyes of age-, sex-, and axial length-matched controls (control group) were analyzed. Corneal videokeratometry and pachymetry were performed using a Scheimpflug tomographer (Pentacam). For measurements of the peripheral cornea and the anterior sclera, a spectral-domain anterior segment optical coherence tomography device (Spectralis) was used. RESULTS The study group comprised 51 eyes and the control group, 50 eyes. The mean central corneal thickness in the keratoconus group was statistically significantly lower than in the control group (447.8 μm ± 57.8 [SD] versus 550.5 ± 35.5 μm) (P < .0001). No significant difference in the mean anterior scleral thickness was found between the keratoconus group and the control group (479.1 ± 43.7 μm versus 474.2 ± 43.0 μm) (P =.57). CONCLUSION Although corneal thinning was observed in keratoconus patients, the anterior scleral stroma thickness in these patients seemed to be similar to that in healthy control eyes.

Scleral thinning after repeated intravitreal injections of antivascular endothelial growth factor agents in the same quadrant

PURPOSE We assessed the effects of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy on scleral architecture using spectral domain anterior segment optical coherence tomography (OCT). METHODS A total of 35 eyes of 35 patients treated with at least 30 intravitreal injections in one eye in the inferotemporal quadrant with ranibizumab or aflibercept and 10 or less intravitreal injections in the fellow eye attending the intravitreal injection clinic were included. Enhanced depth imaging anterior segment OCT was used to measure scleral thickness. For each eye the sclera was measured in four quadrants at 3 mm from the limbus. In addition axial eye length was measured in all subjects using partial coherence interferometry. RESULTS The mean number of intravitreal injections was 42 (range, 30-73) and 1.6 (range, 0-9) in the fellow eyes. In the study eyes with more than 30 injections the average scleral thickness in the inferotemporal quadrant was 568.4 μm (SD ± 66 μm) and 590.6 μm (SD ± 75 μm) in the fellow eyes with 10 or less injections (P = 0.003). The mean average scleral thickness in the other three quadrants (inferonasal, superotemporal, and superonasal) was 536.6 μm in the study eyes (SD ± 100 μm) and 545.2 μm (SD ± 109 μm) in the fellow eyes (P = 0.22). There was a borderline association of the total number of injections with scleral thickness change in the inferotemporal quadrant (r = 0.3, P = 0.052). CONCLUSIONS Intravitreal injections may lead to scleral changes when applied repeatedly in the same quadrant. Thus, alternating the injection site should be considered in patients requiring multiple intravitreal injections.

Morphological changes in the conjunctiva, episclera and sclera following short-term miniscleral contact lens wear in rigid lens neophytes

PURPOSE To quantify the influence of short-term wear of miniscleral contact lenses on the morphology of the corneo-scleral limbus, the conjunctiva, episclera and sclera. METHODS OCT images of the anterior eye were captured before, immediately following 3h of wear and then 3h after removal of a miniscleral contact lens for 10 young (27±5 years) healthy participants (neophyte rigid lens wearers). The region of analysis encompassed 1mm anterior, to 3.5mm posterior to the scleral spur. Natural diurnal variations in thickness were measured on a separate day and compensated for in subsequent analyses. RESULTS Following 3h of lens wear, statistically significant tissue thinning was observed across all quadrants, with a mean decrease in thickness of -24.1±3.6μm (p<0.001), which diminished, but did not return to baseline 3h after lens removal (-16.9±1.9μm, p<0.001). The largest tissue compression was observed in the superior quadrant (-49.9±8.5μm, p<0.01) and in the annular zone 1.5mm from the scleral spur (-48.2±5.7μm), corresponding to the approximate edge of the lens landing zone. Compression of the conjunctiva/episclera accounted for about 70% of the changes. CONCLUSIONS Optimal fitting miniscleral contact lenses worn for three hours resulted in significant tissue compression in young healthy eyes, with the greatest thinning observed superiorly, potentially due to the additional force of the eyelid, with a partial recovery of compression 3h after lens removal. Most of the morphological changes occur in the conjunctiva/episclera layers.

Response of the anterior sclera to accommodation in myopes and emmetropes

• The biomechanical properties of the sclera are documented to be altered in eyes with myopia, with the myopic sclera thought to be more susceptible to deformation from otherwise normal ocular forces. • The close anatomical and functional relationship between the ciliary body and sclera suggests that ciliary muscle contraction during accommodation may influence the overlying sclera. • This study aimed to characterise the changes occurring in anterior scleral thickness with accommodation using anterior segment optical coherence tomography (AS-OCT) in young adult myopes and emmetropes.

Metrics of the normal anterior sclera: imaging with optical coherence tomography

BACKGROUND To investigate anterior scleral thickness in a cohort of healthy subjects using enhanced depth imaging anterior segment optical coherence tomography. METHODS Observational case series. The mean scleral thickness in the inferonasal, inferotemporal, superotemporal, and superonasal quadrant was measured 2 mm from the scleral spur on optical coherence tomography in healthy volunteers. RESULTS Fifty-three eyes of 53 Caucasian patients (25 male and 28 female) with an average age of 48.6 years (range: 18 to 92 years) were analysed. The mean scleral thickness was 571 μm (SD 84 μm) in the inferonasal quadrant, 511 μm (SD 80 μm) in the inferotemporal quadrant, 475 (SD 81 μm) in the superotemporal, and 463 (SD 64 μm) in the superonasal quadrant. The mean scleral thickness was significantly different between quadrants (p < 0.0001, repeated measures one-way ANOVA). The association between average scleral thickness and age was statistically significant (p < 0.0001, Pearson r = 0.704). CONCLUSIONS Enhanced depth imaging optical coherence tomography revealed the detailed anatomy of the anterior sclera and enabled non-invasive measurements of scleral thickness in a non-contact approach. The anterior scleral thickness varies significantly between quadrants, resembling the spiral of Tillaux. An association of increasing scleral thickness with age was found.

Biomechanical aspects of the anterior segment in human myopia

The thesis investigates the relationship between the biomechanical properties of the anterior human sclera and cornea in vivo using Schiotz tonometry (ST), rebound tonometry (RBT, iCare) and the Ocular Response Analyser (ORA, Reichert). Significant differences in properties were found to occur between scleral quadrants. Structural correlates for the differences were examined using Partial Coherent Interferometry (IOLMaster, Zeiss), Optical Coherent tomography (Visante OCT), rotating Scheimpflug photography (Pentacam, Oculus) and 3-D Magnetic Resonance Imaging (MRI). Subject groups were employed that allowed investigation of variation pertaining to ethnicity and refractive error. One hundred thirty-five young adult subjects were drawn from three ethnic groups: British-White (BW), British-South-Asian (BSA) and Hong-Kong-Chinese (HKC) comprising non-myopes and myopes. Principal observations: ST demonstrated significant regional variation in scleral resistance a) with lowest levels at quadrant superior-temporal and highest at inferior-nasal; b) with distance from the limbus, anterior locations showing greater resistance. Variations in resistance using RBT were similar to those found with ST; however the predominantly myopic HKC group had a greater overall mean resistance when compared to the BW-BSA group. OCT-derived scleral thickness measurements indicated the sclera to be thinner superiorly than inferiorly. Thickness varied with distance from the corneolimbal junction, with a decline from 1 to 2 mm followed by a successive increase from 3 to 7 mm. ORA data varied with ethnicity and refractive status; whilst axial length (AL) was associated with corneal biometrics for BW-BSA individuals it was associated with IOP in the HKC individuals. Complex interrelationships were found between ORA Additional-Waveform-Parameters and biometric data provided by the Pentacam. OCT indicated ciliary muscle thickness to be greater in myopia and more directly linked to posterior ocular volume (from MRI) than AL. Temporal surface areas (SAs, from MRI) were significantly smaller than nasal SAs in myopic eyes; globe bulbosity (from MRI) was constant across quadrants.

Diurnal variation of anterior scleral and conjunctival thickness

Purpose To examine whether anterior scleral and conjunctival thickness undergoes significant diurnal variation over a 24-hour period. Methods Nineteen healthy young adults (mean age 22 ± 2 years) with minimal refractive error (mean spherical equivalent refraction -0.08 ± 0.39 D), had measures of anterior scleral and conjunctival thickness collected using anterior segment optical coherence tomography (AS-OCT) at seven measurement sessions over a 24-hour period. The thickness of the temporal anterior sclera and conjunctiva were determined at 6 locations (each separated by 0.5 mm) at varying distances from the scleral spur for each subject at each measurement session. Results Both the anterior sclera and conjunctiva were found to undergo significant diurnal variations in thickness over a 24-hour period (both p <0.01). The sclera and conjunctiva exhibited a similar pattern of diurnal change, with a small magnitude thinning observed close to midday, and a larger magnitude thickening observed in the early morning immediately after waking. The amplitude of diurnal thickness change was larger in the conjunctiva (mean amplitude 69 ± 29 μm) compared to the sclera (21 ± 8 μm). The conjunctiva exhibited its smallest magnitude of change at the scleral spur location (mean amplitude 56 ± 17 μm) whereas the sclera exhibited its largest magnitude of change at this location (52 ± 21 μm). Conclusions This study provides the first evidence of diurnal variations occurring in the thickness of the anterior sclera and conjunctiva. Studies requiring precise measures of these anatomical layers should therefore take time of day into consideration. The majority of the observed changes occurred in the early morning immediately after waking and were of larger magnitude in the conjunctiva compared to the sclera. Thickness changes at other times of the day were of smaller magnitude and generally not statistically significant.

Comparative effects of posterior eye cup tissues from Myopic and Hyperopic chick eyes on cultured scleral fibroblasts

The role of individual ocular tissues in mediating changes to the sclera during myopia development is unclear. The aim of this study was to examine the effects of retina, RPE and choroidal tissues from myopic and hyperopic chick eyes on the DNA and glycosaminoglycan (GAG) content in cultures of chick scleral fibroblasts. Primary cultures of fibroblastic cells expressing vimentin and -smooth muscle actin were established in serum-supplemented growth medium from 8-day-old normal chick sclera. The fibroblasts were subsequently co-cultured with posterior eye cup tissue (full thickness containing retina, RPE and choroid) obtained from untreated eyes and eyes wearing translucent diffusers (form-deprivation myopia, FDM) or -15D lenses (lens-induced myopia, LIM) for 3 days (post hatch day 5 to 8) (n=6 per treatment group). The effect of tissues (full thickness and individual retina, RPE, and choroid layers) from -15D (LIM) versus +15D (lens-induced hyperopia, LIH) treated eyes was also determined. Refraction changes in the direction predicted by the visual treatments were confirmed by retinoscopy prior to tissue collection. Glycosaminoglycan (GAG) and DNA content of the scleral fibroblast cultures were measured using GAG and PicoGreen assays. There was no significant difference in the effect of full thickness tissue from either FDM or LIM treated eyes on DNA and GAG content of scleral fibroblasts (DNA 8.9±2.6 µg and 8.4±1.1 µg, p=0.12; GAG 11.2±0.6 µg and 10.1±1.0 µg, p=0.34). Retina from LIM eyes did not alter fibroblast DNA or GAG content compared to retina from LIH eyes (DNA 27.2±1.7 µg versus 23.2±1.5 µg, p=0.21; GAG 28.1±1.7 µg versus. 28.7±1.2 µg, p=0.46). Similarly, the choroid from LIH and LIM eyes did not produce a differential effect on DNA content (DNA, LIM 46.9±6.4 versus LIH 51.5±4.7 µg, p=0.31), whereas GAG content was higher for cells in co-culture with choroid from LIH eyes (GAG 32.5±0.7 µg versus 18.9±1.2 µg, F1,6=9.210, p=0.0002). In contrast, fibroblast DNA was greater in co-culture with RPE from LIM eyes than the empty basket and DNA content less for co-culture with RPE from LIH eyes (LIM: 72.4±6.3 µg versus Empty basket: 46.03±1.0 µg; F1,6=69.99, p=0.0005 and LIH: 27.9±2.3 µg versus empty basket: 46.03±1.0 µg; p=0.0004). GAG content was higher with RPE from LIH eyes (LIH: 33.7±1.9 µg versus empty basket: 29.5±0.8 µg, F1,6=13.99, p=0.010) and lower with RPE from LIM eyes (LIM: 27.7±0.9 µg versus empty basket: 29.5±0.8 µg, p=0.021). GAG content of cells in co-culture with choroid from LIH eyes was higher compared to co-culture with choroid from LIM eyes (32.5±0.7 µg versus 18.9±1.2 µg respectively, F1,6=9.210, p=0.0002). In conclusion, these experiments provide evidence for a directional growth signal that is present (and remains) in the ex-vivo RPE, but that does not remain in the ex-vivo retina. The identity of this factor(s) that can modify scleral cell DNA and GAG content requires further research.

Choroidal thickness in childhood

Purpose To examine choroidal thickness (ChT) and its spatial distribution across the posterior pole in pediatric subjects with normal ocular health and minimal refractive error. Methods ChT was assessed using spectral domain optical coherence tomography (OCT) in 194 children aged between 4-12 years, with spherical equivalent refractive errors between +1.25 and -0.50 DS. A series of OCT scans were collected, imaging the choroid along 4 radial scan lines centered on the fovea (each separated by 45°). Frame averaging was used to reduce noise and enhance chorio-scleral junction visibility. The transverse scale of each scan was corrected to account for magnification effects associated with axial length. Two independent masked observers manually segmented the OCT images to determine ChT at foveal centre, and averaged across a series of perifoveal zones over the central 5 mm. Results The average subfoveal ChT was 330 ± 65 µm (range 189-538 µm), and was significantly influenced by age (p=0.04). The ChT of the 4 to 6 year old age group (312 ± 62 µm) was significantly thinner compared to the 7 to 9 year olds (337 ± 65 µm, p<0.05) and bordered on significance compared to the 10 to 12 year olds (341 ± 61 µm, p=0.08). ChT also exhibited significant variation across the posterior pole, being thicker in more central regions. The choroid was thinner nasally and inferiorly compared to temporally and superiorly. Multiple regression analysis revealed age, axial length and anterior chamber depth were significantly associated with subfoveal ChT (p<0.001). Conclusions ChT increases significantly from early childhood to adolescence. This appears to be a normal feature of childhood eye growth.

Hypoxic corneal changes following 8 hours of scleral contact lens wear

- Purpose To examine the change in corneal thickness and posterior curvature following 8 hours of miniscleral contact lens wear. - Methods Scheimpflug imaging (Pentacam HR, Oculus) was captured before, and immediately following, 8 hours of miniscleral contact lens wear for 15 young (mean age 22 ± 3 years), healthy participants with normal corneae. Natural diurnal variations were considered by measuring baseline corneal changes obtained on a separate control day without contact lens wear. - Results Over the central 6 mm of the cornea, a small, but highly statistically significant amount of edema was observed following 8 hours of miniscleral lens wear, after accounting for normal diurnal fluctuations (mean ± standard deviation percentage swelling 1.70 ± 0.98%, p < 0.0001). Posterior corneal topography remained stable following lens wear (-0.01 ± 0.07 mm steepening over the central 6 mm, p = 0.60). The magnitude of posterior corneal topographical changes following lens wear did not correlate with the extent of lens-related corneal edema (r = -0.16, p = 0.57). Similarly, the initial central corneal vault (maximum post-lens tear layer depth) was not associated with corneal swelling following lens removal (r = 0.27, p = 0.33). - Conclusions While a small amount of corneal swelling was induced following 8 hours of miniscleral lens wear (on average <2%), modern high Dk miniscleral contact lenses that vault the cornea do not induce clinically significant corneal edema or hypoxic related posterior corneal curvature changes during short-term wear. Longer-term studies of compromised eyes (e.g. corneal ectasia) are still required to inform the optimum lens and fitting characteristics for safe scleral lens wear to minimize corneal hypoxia.

Senile scleral plaques imaged with enhanced depth optical coherence tomography

PURPOSE Senile scleral plaques (SSP) are sharply demarcated greyish areas located just anterior to the insertions of the horizontal rectus muscles and thus are frequently encountered during transscleral intravitreal injections. The aim of this study was to characterize SSP using enhanced depth imaging spectral domain anterior segment optical coherence tomography (OCT) in a cohort of patients attending intravitreal injection clinics. METHODS Prospective cross-sectional study of 380 patients attending the clinic for intravitreal injections at the Department of Ophthalmology at the Bern University Hospital. Thirty-two patients with SSP were identified and the anatomical features were assessed using anterior segment OCT. RESULTS In our patient cohort, we found a SSP prevalence of 8.2%. Senile scleral plaques were easily identifiable using anterior segment OCT and were found at the insertion sites of the horizontal recti muscles. The mean horizontal diameter was 2.2 mm (±760 μm SD), the mean vertical diameter was 3.3 mm (±144 μm SD), and the average surface area was 5.3 mm(2) (±0.4 mm(2) SD). The mean senile scleral plaque thickness was 0.6 mm (±149 μm SD). The mean distance from the limbus was 2.24 mm for nasally located SSP and 3.22 mm for temporally located SSP. CONCLUSION SSP are frequently encountered during intravitreal injections as they are located just anterior to the insertion sites of the horizontal recti muscles. Because the scleral stroma is rarefied and due to calcifications within SSP, these areas should be avoided when performing multiple intravitreal injections as this may result in rupture of the sclera.

Ocular biometric correlates of ciliary muscle thickness in human myopia

Purpose - Anterior segment optical coherent tomography (AS-OCT) is used to further examine previous reports that ciliary muscle thickness (CMT) is increased in myopic eyes. With reference to temporal and nasal CMT, interrelationships between biometric and morphological characteristics of anterior and posterior segments are analysed for British-White and British-South-Asian adults with and without myopia. Methods - Data are presented for the right eyes of 62 subjects (British-White n = 39, British-South-Asian n = 23, aged 18–40 years) with a range of refractive error (mean spherical error (MSE (D)) -1.74 ± 3.26; range -10.06 to +4.38) and separated into myopes (MSE (D) <-0.50, range -10.06 to -0.56; n = 30) and non-myopes (MSE (D) =-0.50, -0.50 to +4.38; n = 32). Temporal and nasal ciliary muscle cross-sections were imaged using a Visante AS-OCT. Using Visante software, manual measures of nasal and temporal CMT (NCMT and TCMT respectively) were taken in successive posterior 1 mm steps from the scleral spur over a 3 mm distance (designated NCMT1, TCMT1 et seq). Measures of axial length and anterior chamber depth were taken with an IOLMaster biometer. MSE and corneal curvature (CC) measurements were taken with a Shin-Nippon auto-refractor. Magnetic resonance imaging was used to determine total ocular volume (OV) for 31 of the original subject group. Statistical comparisons and analyses were made using mixed repeated measures anovas, Pearson's correlation coefficient and stepwise forward multiple linear regression. Results - MSE was significantly associated with CMT, with thicker CMT2 and CMT3 being found in the myopic eyes (p = 0.002). In non-myopic eyes TCMT1, TCMT2, NCMT1 and NCMT2 correlated significantly with MSE, AL and OV (p < 0.05). In contrast, myopic eyes failed generally to exhibit a significant correlation between CMT, MSE and axial length but notably retained a significant correlation between OV, TCMT2, TCMT3, NCMT2 and NCMT3 (p < 0.05). OV was found to be a significantly better predictor of TCMT2 and TCMT3 than AL by approximately a factor of two (p < 0.001). Anterior chamber depth was significantly associated with both temporal and nasal CMT2 and CMT3; TCMT1 correlated positively with CC. Ethnicity had no significant effect on differences in CMT. Conclusions - Increased CMT is associated with myopia. We speculate that the lack of correlation in myopic subjects between CMT and axial length, but not between CMT and OV, is evidence that disrupted feedback between the fovea and ciliary apparatus occurs in myopia development.