Biomechanical properties measured with dynamic Scheimpflug analyzer in central serous chorioretinopathy.

PURPOSE: Recent evidence suggests that venous congestion at the vortex vein significantly contributes to the development of central serous chorioretinopathy (CSCR), and sclera is observed to be thicker in affected eyes. This study aims to investigate whether eyes with CSCR exhibit stiff corneas, measured using Corneal Visualization Scheimflug Technology (Corvis ST), which may serve as an indicator of scleral stiffness. METHODS: This retrospective case-control study comprises 52 eyes from 33 patients diagnosed with CSCR and 52 eyes from 32 normal controls without CSCR. We compared biomechanical parameters measured with Corvis ST and anterior scleral thickness measured using anterior segment swept-source optical coherence tomography between the two groups. RESULTS: Age, sex, axial length, intraocular pressure, and central corneal thickness showed no significant differences between the two groups (p > 0.05, linear mixed model). Three biomechanical parameters-peak distance, maximum deflection amplitude, and integrated inverse radius-indicated less deformability in CSCR eyes compared to control eyes. The stress-strain index (SSI), a measure of stiffness, and anterior scleral thickness (AST) at temporal and nasal points were significantly higher in the CSCR eyes. SSI and AST were not correlated, yet both were significantly and independently associated with CSCR in a multivariate logistic regression model. CONCLUSIONS: Eyes affected by CSCR have stiffer corneas, irrespective of thicker scleral thickness. This suggests that stiffer sclera may play a role in the pathogenesis of CSCR.

Interplay between intraocular and intracranial pressure effects on the optic nerve head in vivo.

Intracranial pressure (ICP) has been proposed to play an important role in the sensitivity to intraocular pressure (IOP) and susceptibility to glaucoma. However, the in vivo effects of simultaneous, controlled, acute variations in ICP and IOP have not been directly measured. We quantified the deformations of the anterior lamina cribrosa (ALC) and scleral canal at Bruch's membrane opening (BMO) under acute elevation of IOP and/or ICP. Four eyes of three adult monkeys were imaged in vivo with OCT under four pressure conditions: IOP and ICP either at baseline or elevated. The BMO and ALC were reconstructed from manual delineations. From these, we determined canal area at the BMO (BMO area), BMO aspect ratio and planarity, and ALC median depth relative to the BMO plane. To better account for the pressure effects on the imaging, we also measured ALC visibility as a percent of the BMO area. Further, ALC depths were analyzed only in regions where the ALC was visible in all pressure conditions. Bootstrap sampling was used to obtain mean estimates and confidence intervals, which were then used to test for significant effects of IOP and ICP, independently and in interaction. Response to pressure manipulation was highly individualized between eyes, with significant changes detected in a majority of the parameters. Significant interactions between ICP and IOP occurred in all measures, except ALC visibility. On average, ICP elevation expanded BMO area by 0.17 mm2 at baseline IOP, and contracted BMO area by 0.02 mm2 at high IOP. ICP elevation decreased ALC depth by 10 µm at baseline IOP, but increased depth by 7 µm at high IOP. ALC visibility decreased as ICP increased, both at baseline (-10%) and high IOP (-17%). IOP elevation expanded BMO area by 0.04 mm2 at baseline ICP, and contracted BMO area by 0.09 mm2 at high ICP. On average, IOP elevation caused the ALC to displace 3.3 µm anteriorly at baseline ICP, and 22 µm posteriorly at high ICP. ALC visibility improved as IOP increased, both at baseline (5%) and high ICP (8%). In summary, changing IOP or ICP significantly deformed both the scleral canal and the lamina of the monkey ONH, regardless of the other pressure level. There were significant interactions between the effects of IOP and those of ICP on LC depth, BMO area, aspect ratio and planarity. On most eyes, elevating both pressures by the same amount did not cancel out the effects. Altogether our results show that ICP affects sensitivity to IOP, and thus that it can potentially also affect susceptibility to glaucoma.

Preserved corneal lamellar transplantation for infectious and noninfectious scleral defects: Three case reports and literature review.

RATIONALE: : Reinforcement of thinned or necrotizing sclera has been conducted using various materials, including allogeneic sclera, allogenic cornea, amniotic membrane, fascia lata, pericardium, periosteum, and perichondrium. Among them, good outcomes have traditionally been obtained using preserved scleral grafts. However, scleral patch grafts have complications such as graft retraction, thinning, dehiscence, and necrosis. Furthermore, to promote epithelial healing, scleral patch grafting must be accompanied by procedures such as amniotic membrane transplantation (AMT) or grafting using conjunctival flaps or autografts. Recently, acellular preserved human corneas have been used in various ophthalmic surgeries, with emerging evidence supporting its use for treating scleral defects as an option that does not require AMT or conjunctival autografting. We investigated whether corneal patch grafting would show wound healing and tectonic success rate outcomes comparable to those of existing techniques. PATIENT PRESENTATION: : Three patients presented with intractable ocular pain. Slit-lamp examination showed marked scleral thinning at the nasal side. DIAGNOSIS: : Scleral thinning progressed with conservative treatment; microbial staining and culturing were performed. Infectious or non-infectious scleritis was diagnosed according to slit-lamp examination and microbial culture results. INTERVENTIONS: : A preserved corneal lamellar patch was grafted at the scleral thinning area. OUTCOMES: All patients achieved tectonic success with reduction of inflammation following corneal patch grafting. Two patients achieved complete re-epithelialization within 7 days, while 25 days were required for the third patient. No patients experienced graft thinning, rejection, or infection. LESSONS: : Our report suggests the feasibility of using acellular preserved human cornea patch grafts to reinforce inflammatory scleral defects and obtain successful outcomes in terms of wound healing. This technique shows a comparable tectonic success rate and superior effect on scleral defect healing without the need for adjunctive AMT or conjunctival autografting.

Biomechanics of the optic nerve head and sclera in canine glaucoma: A brief review.

Glaucoma is a leading cause of irreversible blindness, a progressive optic neuropathy with retinal ganglion cell (RGC) death beginning in the optic nerve head (ONH). A primary risk factor for developing glaucoma is elevated intraocular pressure (IOP). Reducing IOP is the only treatment proven to be effective at delaying disease progression. Nevertheless, even when patients have their IOP reduced, the majority of them continue to lose vision. There are, in both humans and dogs, significant interindividual variabilities in susceptibilities to IOP-induced optic nerve damage. Vision loss progresses much more slowly in Beagles with open-angle glaucoma (OAG) caused by ADAMTS10 mutation. This can be attributed to the mutation-related altered ocular biomechanical properties. The principal site of optic nerve (ON) damage in glaucoma is the ONH. It is suggested that the biomechanical properties of the ONH and the surrounding peripapillary sclera (PPS) contribute to glaucoma development and progression. As far as the beneficial biomechanical properties of the ONH and PPS for a decreased susceptibility and slow progression of glaucoma, data are inconsistent and conflicting. Recent biomechanical studies on beagles with ADAMTS10 mutation demonstrated that the mutant dogs have mechanically weak posterior sclera. This weakness was associated with a reduced collagen density and a lower proportion of insoluble collagen. These changes, observed before glaucoma development, were considered intrinsic characteristics caused by the mutation rather than a secondary effect of IOP elevation. Further studies of ADAMTS10-OAG may elucidate the effects of altered biomechanical properties of ONH and PPS in determining the glaucoma progression.

Isolation and characterization of novel primary cells from the human distal outflow pathway.

Ocular hypertension occurs due to increased resistance to aqueous humor removal through the conventional outflow pathway. Unlike the proximal region of the conventional outflow pathway, the distal region has not been well studied, mostly due to lack of model systems. Here we describe isolation and characterization of human primary vascular distal outflow pathway (VDOP) cells from the distal region of the conventional outflow pathway. Tissue from the distal region was isolated from human corneo-scleral rims, digested with collagenase type I (100 U/ml) and placed on gelatin coated plates to allow cellular growth in Dulbecco's Modified Eagle's Medium (low glucose) containing fetal bovine serum and antibiotic/antimycotic. VDOP cells showed consistent proliferation for up to 7 passages, retained endothelial-like nature of the parent tissues and showed a unique marker phenotype of Lectin+VEGFR2-CD34-NG2- that was distinct from neighboring trabecular meshwork (Lectin+VEGFR2-CD34-NG2+) and Schlemm's canal (Lectin+VEGFR2+CD34+NG2+) cells. Dexamethasone treated VDOP cells did not express myocilin and did not form cross-linked actin networks, in contrast to trabecular meshwork cells. These data show that VDOP cells are unique to the distal outflow region and can be used as a viable in vitro model system to understand the biology of the distal outflow pathway and intraocular pressure regulation.

Anterior scleral thickness and shape changes with different levels of simulated convergence.

PURPOSE: Convergence plays a fundamental role in the performance of near visual tasks. We measured the effect of two levels of convergence on anterior scleral thickness and shape in emmetropes, low to moderate myopes and high myopes. METHODS: Forty-five healthy young adults aged between 18 and 35 years including 15 emmetropes, 15 low/moderate myopes, and 15 high myopes were recruited. Anterior segment optical coherence tomography and eye surface profilometry were used to evaluate the anterior scleral thickness (nasal only, n = 42) and shape (n = 40), before and during two visual tasks involving 9° and 18° convergence, in those participants with complete and reliable data. RESULTS: Convergence led to a thickening of the total anterior eye wall (5.9 ± 1.4 µm) and forward movement (10 ± 2 µm) of the nasal anterior scleral surface (both p < 0.001). Larger changes were found at 18° than at 9° convergence and in more peripheral nasal scleral regions. There was a significant association between total wall thickening and forward movement of the scleral surface. Refractive group was not a significant main effect, but there were significant interactions between refractive group and the thickness changes with convergence in different scleral regions. CONCLUSION: During convergence, the biomechanical forces acting on the eye lead to nasal anterior scleral thickening and forward movement of the nasal scleral surface.

In vivo measures of anterior scleral resistance in humans with rebound tonometry.

PURPOSE: To measure regional variations in anterior scleral resistance (ASR) using a ballistic rebound tonometer (RBT) and examine whether the variations are significantly affected by ethnicity and refractive error (RE). METHODS: ASR was measured using a RBT (iCare TA01) following calibration against the biomechanical properties of agarose biogels. Eight scleral regions (nasal, temporal, superior, inferior, inferior-nasal, inferior-temporal, superior-nasal and superior-temporal) were measured at locations 4mm from the limbus. Subjects were 130 young adults comprising three ethnic groups whose RE distributions [MSE (D) ± S.D.] incorporated individuals categorised as without-myopia (NM; MSE ≥ -0.50) and with-myopia (WM; MSE < -0.50); British-White (BW): 26 NM + 0.52 ± 1.15D; 22 WM -3.83 ± 2.89D]; British-South-Asian (BSA): [9 NM + 0.49 ± 1.06D; 11 WM -5.07 ± 3.76D; Hong-Kong-Chinese (HKC): [11 NM + 0.39 ± 0.66D; 49 WM -4.46 ± 2.70D]. Biometric data were compiled using cycloplegic open-field autorefraction and the Zeiss IOLMaster. Two- and three-way repeated measures analysis of variances (anovas) tested regional differences for RBT values across both refractive status and ethnicity whilst stepwise forward multiple linear regression was used as an exploratory test. RESULTS: Significant regional variations in ASR were identified for the BW, BSA and HKC (p < 0.001) individuals; superior-temporal region showed the lowest levels of resistance whilst the inferior-nasal region the highest. Compared to the BW and BSA groups, the HKC subjects displayed a significant increase in mean resistance for each respective region (p < 0.001). With the exception of the inferior region, ethnicity was found to be the chief predictor for variation in the scleral RBT values for all other regions. Mean RE group differences were insignificant. CONCLUSIONS: The novel application of RBT to the anterior sclera confirm regional variation in ASR. Greater ASR amongst the HKC group than the BW and BSA individuals suggests that ethnic differences in anterior scleral biomechanics may exist.

Treatment effect of posterior scleral reinforcement on controlling myopia progression: A systematic review and meta-analysis.

BACKGROUND: High myopia is a sight-threatening disease that causes axial length elongation and severe complications. Data on the benefits of posterior scleral reinforcement surgery in myopia control have been conflicting. The purpose of this study was to explore the treatment effect and complications of posterior scleral reinforcement in the treatment of myopia. METHODS: Articles were retrieved for relevant studies from inception to July 24, 2019, by PubMed, EMBASE, and Ovid. Analyses were conducted to compare the treatment effects of controlling spherical equivalent refraction and axial length elongation. The weighted mean difference and Hedges' adjusted g were used to evaluate the treatment effects, with a random-effects model. Heterogeneity was quantified using I2 statistic and explored by subgroup analysis. Publication bias was addressed by funnel plots and Egger's test. RESULTS: A total of 11 articles were included in this meta-analysis. On estimating the treatment effect, the mean differences of myopia progression and axial length changes between surgery and control groups were 0.41 diopters per year (95% CI 0.21 to 0.61; P < .001) and -0.17 mm per year (95% CI -0.22 to -0.11; P < .001). Subgroup analysis showed significant treatment effects of the single wide strip operation. Single-arm meta-analysis showed less annual axial elongation in children subgroup. These results were robust by sensitivity analysis. The incidence of some major complications in the operation group were significantly greater (5.8% vs 2.7% for myopic degeneration; 2.3% vs 1.6% for macular hemorrhage; 0.8% vs 0 for retinal detachment). CONCLUSION: Posterior scleral reinforcement may be an effective surgery on controlling myopia progression by slowing both refraction and axial length change. However, frequent surgical complications should be considered. Further well-designed studies are needed to determine the long-term safety and efficacy.

New retinal tack designs: an analysis of retention forces in human scleral tissue.

PURPOSE: The study aimed to construct a new retinal tack design with high retention forces to prevent spontaneous disentanglement in cases of complicated retinal surgery. METHODS: Six new forms for the peak of a retinal tack were developed using computer-aided design (CAD); then a prototype was produced for each model. Finally, standardised design testing was conducted using human (ex vivo) sclera by logging 15 consecutive measurements for each model. RESULTS: Seven different models underwent pull-out testing (six new models and the original tack model), but two tack models (Model 4, Model 5) failed to penetrate the human tissue. The highest pull-out forces (median) were measured for Model 3, followed by Model 6, Model 2 and Model 1. The original Heimann tack (Model H) was found to have the lowest retention forces. CONCLUSION: The different tack designs altered the penetration and holding forces. The retention forces of the proposed peak design led to a significant increase in the retention forces that were more than twice as high as those in the original Heimann Model.

Biomechanical properties of the rat sclera obtained with inverse finite element modeling.

It is widely accepted that biomechanics plays an important role in glaucoma pathophysiology, but the mechanisms involved are largely unknown. Rats are a common animal model of glaucoma, and finite element models are being developed to provide much-needed insight into the biomechanical environment of the posterior rat eye. However, material properties of rat ocular tissues, including the sclera, are currently unknown. Since the sclera plays a major role in posterior ocular biomechanics, our goal was to use inverse finite element modeling to extract rat scleral material properties. We first used digital image correlation to measure scleral surface displacement during whole-globe inflation testing. We modeled the sclera as a nonlinear material with embedded collagen fibers and then fit modeled displacements to experimental data using a differential evolution algorithm. Subject-specific models were constructed in which 3 parameters described the stiffness of the ground substance and collagen fibers in the posterior eye, and 16 parameters defined the primary orientation and alignment of fibers within eight scleral sub-regions. We successfully extracted scleral material properties for eight rat eyes. Model displacements recreated general patterns of the experimental displacements but did not always match local patterns. The fiber directions and fiber concentration parameters were highly variable, but on average, fibers were aligned circumferentially and were more aligned in the peripapillary sclera than in the peripheral sclera. The material properties determined here will be used to inform future finite element models of the rat posterior eye with the goal of elucidating the role of biomechanics in glaucoma pathophysiology.

The contribution of sGAGs to stress-controlled tensile response of posterior porcine sclera.

Despite the significant progress in characterizing mechanical functions of individual scleral extracellular matrix (ECM) components, the biomechanical contribution of sulfated glycosaminoglycans (sGAGs) is still poorly understood. The primary purpose of this study was to determine the possible function of sGAGs in scleral mechanical response by characterizing the tensile behavior of normal and sGAG-depleted samples. We used chondroitinase ABC solution to remove sGAGs from scleral samples that were dissected from posterior porcine eyes. We performed biochemical analyses for assessing the efficacy of sGAG removal protocol. Furthermore, we conducted stress-controlled uniaxial tensile tests to characterize the influence of sGAG removal on mechanical properties of sclera. The tensile behavior of scleral strips right after dissection and after being soaked in buffer was also determined. Biochemical analyses confirmed that 18 hour incubation in 0.125 U/ml Chondroitinase ABC solution removed over 90% of chondroitin and dermatan sGAGs. No significant difference was observed in the thickness/hydration of samples because of enzyme- and buffer-treated samples. Furthermore, it was found that sGAG depletion did not significantly alter the tangent modulus, energy dissipation, and peak strain of posterior scleral strips. It was concluded that sGAGs did not influence the stress-controlled viscoelastic tensile response of sclera.

Regulatory roles of differentially expressed MicroRNAs in metabolic processes in negative Lens-induced myopia Guinea pigs.

BACKGROUND: Myopia is one of the most common vision defects worldwide. microRNAs can regulate the target gene expression, influencing the development of diseases. RESULTS: To investigate the alterations of microRNA profiling in negative lens-induced myopia (NLIM) guinea pigs and to explore the regulatory role of microRNAs in the occurrence and the development of myopia, we first established the NLIM guinea pig model after induction for 2 weeks. Further, we isolated sclera to purify total messenger RNA (mRNA) in both NLIM and NLIM fellow sclera. Using next generation sequencing technique and bioinformatics analysis, we identified the differentially expressed microRNAs in NLIM guinea pigs, performed the bioinformatics annotation for the differentially expressed microRNAs, and validated the expression of differentially expressed microRNAs. As a result, we successfully established an NLIM model in guinea pigs, identified 27 differentially expressed microRNAs in NLIM guinea pig sclera, including 10 upregulated and 17 downregulated microRNAs. The KEGG annotation showed the main signaling pathways were closely associated with PPAR signaling, pyruvate and propanoate metabolisms, and TGF-beta signaling pathways. CONCLUSIONS: Our findings indicate that the development of myopia is mainly involved in the disorder of metabolic processes in NLIM guinea pigs. The PPAR signaling, pyruvate and propanoate metabolism pathways may play roles in the development of myopia.

Scleral structure and biomechanics.

As the eye's main load-bearing connective tissue, the sclera is centrally important to vision. In addition to cooperatively maintaining refractive status with the cornea, the sclera must also provide stable mechanical support to vulnerable internal ocular structures such as the retina and optic nerve head. Moreover, it must achieve this under complex, dynamic loading conditions imposed by eye movements and fluid pressures. Recent years have seen significant advances in our knowledge of scleral biomechanics, its modulation with ageing and disease, and their relationship to the hierarchical structure of the collagen-rich scleral extracellular matrix (ECM) and its resident cells. This review focuses on notable recent structural and biomechanical studies, setting their findings in the context of the wider scleral literature. It reviews recent progress in the development of scattering and bioimaging methods to resolve scleral ECM structure at multiple scales. In vivo and ex vivo experimental methods to characterise scleral biomechanics are explored, along with computational techniques that combine structural and biomechanical data to simulate ocular behaviour and extract tissue material properties. Studies into alterations of scleral structure and biomechanics in myopia and glaucoma are presented, and their results reconciled with associated findings on changes in the ageing eye. Finally, new developments in scleral surgery and emerging minimally invasive therapies are highlighted that could offer new hope in the fight against escalating scleral-related vision disorder worldwide.

Association between peripapillary scleral deformation and choroidal microvascular circulation in glaucoma.

Peripapillary vessel density, which is reduced in eyes with glaucoma, has been proposed as a diagnostic tool for the desease and peripapillary choroidal microvasculature dropout(MvD) is considered one of pathophysiological manifestation of glaucomatous damage. However, little is known about the underlying pathogenic mechanism of dropout. According to recent studies, MvD is associated with structural changes in ONH structures. Therefore, we investigated the association between peripapillary scleral deformation and MvD. Data from 62 open-angle glaucoma (OAG) eyes with MvD and 36 eyes without MvD were analyzed in this study. And eyes with MvD were classified into two groups based on location: a juxtapapillary group and a non-juxtapapillary group for further analysis. More eyes with MvD had focal scleral deformation than did those without MvD (64.5% versus 2.8%; P < 0.001). Peripapillary choroidal thickness and focal scleral deformation were significantly associated with MvD. And juxtapapillary group was more associated with focal scleral deformation and coincidental RNFL defects than non-juxtapapillary groups. Peripapillary choroidal MvD was associated with the presence of scleral deformation, especially with juxtapapillary MvD, which was related to corresponding RNFL defects.

Sutureless transconjunctival intrascleral intraocular lens fixation: the modified Yamane technique / Fixação de lente intraocular intraescleral transconjuntival sem sutura: técnica de Yamane modificada

ABSTRACT Purpose: To evaluate the efficacy and safety of the modified Yamane technique with sutureless transconjunctival intrascleral intraocular lens fixation. Methods: Sutureless transconjunctival intrascleral haptic fixated intraocular lens implantation was performed in patients with aphakia and dislocated intraocular lenses. A clear corneal incision (2.8 mm) was made into the temporal quadrant and a three-piece intraocular lens was implanted into the anterior chamber. The haptics of the intraocular lens were externalized with a 27 G needle via transconjunctival scleral tunnels at the 6 and 12 o'clock positions. The transconjunctival scleral tunnels were prepared to conform to the haptic position and curvature. The site of the scleral tunnels was 2mm from the limbus with a length of 2 mm in the sclera and was aimed at the end of the posterior chamber. The tips of the haptics were cauterized to create a terminal knob. The haptics were pushed back and the knobs were implanted into the scleral tunnels. Results: The study cohort included 21 patients with unilateral aphakia and dislocated intraocular lenses. All patients were examined postoperatively and at postoperative day 1, day 7, month 1, and month 3. All examinations revealed formation of the anterior chamber and well-centralized intraocular lenses. No haptic-related complications of exposure, foreign body sensation, or discomfort were observed. Conclusion: Sutureless transconjunctival intrascleral haptic fixated intraocular lensimplantation is an effective, safe, and practical surgical alternative. This technique was superior to the Yamane method with regard to comfort and surgical duration. Further studies with longer follow-up evaluations are warranted to verify long-term complications.

RESUMO Objetivo: Avaliar a eficácia e a segurança da técnica de Yamane modificada com a fixação de lenta intraocular transconjuntival sem sutura. Métodos: O implante de lente intraocular intraescleral e transconjuntival sem sutura foi realizado em pacientes com afacia e lentes intraoculares luxadas. Uma incisão em córnea clara (2,8 mm) foi feita no quadrante temporal e uma lente intraocular de três peças foi implantada na câmara anterior. Os hápticos da lente intraocular foram externalizados com uma agulha 27G através de túneis esclerais transconjuntivais nas posições de 6 e 12 horas. Os túneis esclerais transconjuntivais foram preparados para se ajustarem à posição e curvatura hápticas. O local dos túneis esclerais foi de 2 mm do limbo com um comprimento de 2 mm na esclera e foi destinado ao final da câmara posterior. As pontas dos hápticos foram cauterizadas para criar uma saliência terminal. Os hápticos foram empurrados para tras e as saliências foram implantadas nos túneis esclerais. Resultados: A coorte do estudo incluiu 21 pacientes com afacia unilateral e lentes intraocular deslocada. Todos os pacientes foram examinados no pós-operatório e no dia 1, 7, 1 mês e 3 meses do pós-operatório. Todos os exames revelaram formação da uma câmara anterior e lentes intraoculares bem centralizadas. Nenhuma complicação hápticas relacionada à exposição, sensação de corpo estranho ou desconforto foram observadas. Conclusão: O implante de lente intraocular transconjuntival intraescleral sem sutura é uma alternativa cirúrgica eficaz, segura e prática. Esta técnica foi superior ao método de Yamane no que diz respeito ao conforto e duração cirúrgica. Mais estudos com avaliações de seguimento mais prolongados são necessários para verificar as complicações de longo prazo.

Regional changes in the elastic properties of myopic Guinea pig sclera.

Biomechanical changes in the sclera likely underlie the excessive eye elongation of axial myopia. We studied the biomechanical characteristics of myopic sclera at the microscopic level using scanning acoustic microscopy (SAM) with 7-µm in-plane resolution. Guinea pigs underwent form-deprivation (FD) in one eye from 4 to 12 days of age to induce myopia, and 12-µm-thick scleral cryosections were scanned using a custom-made SAM. Two-dimensional maps of the bulk modulus (K) and mass density (ρ) were derived from the SAM data using a frequency-domain approach. We assessed the effect on K and ρ exerted by: 1) level of induced myopia, 2) region (superior, inferior, nasal or temporal) and 3) eccentricity from the nerve using univariate and multivariate regression analyses. Induced myopia ranged between -3D and -9.3D (Mean intraocular difference of -6.2 ±â€¯1.7D, N = 11). K decreased by 0.036 GPa for every 1.0 D increase in induced myopia across vertical sections (p < 0.001). Among induced myopia right eyes, K values in the inherently more myopic superior region were 0.088 GPa less than the inferior region (p = 0.002) and K in the proximal nasal region containing the central axis were 0.10 GPa less than temporal K (p = 0.036). K also increased 0.12 GPa for every 1 mm increase in superior vertical distance (p < 0.001), an effect that was blunted after 1 week of FD. Overall, trends for ρ were less apparent than for K. ρ values increased by 20.7 mg/cm3 for every 1.00 D increase in induced myopia across horizontal sections (p < 0.001), and were greatest in the region containing the central posterior pole. ρ values in the inherently more myopic superior region were 13.1 mg/cm3 greater than that found in inferior regions among control eyes (p = 0.002), and increased by 11.2 mg/cm3 for every 1 mm increase in vertical distance (p = 0.001). This peripheral increase in ρ was blunted after 1 week of FD. Scleral material properties vary depending on the location in the sclera and the level of induced myopia. Bulk modulus was most reduced in the most myopic regions (both induced myopia and inherent regional myopia), and suggests that FD causes microscopic local decreases in sclera stiffness, while scleral mass density was most increased in the most myopic regions.

Gene expression signatures in tree shrew sclera during recovery from minus-lens wear and during plus-lens wear.

Purpose: In juvenile tree shrews that have developed minus lens-induced myopia, if lens treatment is discontinued, refractive recovery (REC) occurs. However, in age-matched juvenile animals, plus-lens wear (PLW) produces little refractive change, although the visual stimulus (myopia) is similar (an "IGNORE" response). Because the sclera controls axial elongation and refractive error, we examined gene expression in the sclera produced by PLW and compared it with the gene expression signature produced by REC to learn whether these similar refractive conditions produce similar, or differing, scleral responses. Methods: Eight groups of tree shrews (n = 7 per group) were examined. Four groups wore a monocular -5 D lens for 11 days until 35 days of visual experience (DVE). Lens wear was then discontinued, and the animals recovered for 0 h (REC-0), 2 h (REC-2h), 1 day (REC-1d), or 4 days (REC-4d). Starting at 35 DVE, three groups wore a monocular +5 D lens for 2 h (PLW-2h), 1 day (PLW-1d), or 4 days (PLW-4d). A normal group (PLW-0) was examined at 38 DVE to provide baseline measures. Using quantitative real-time PCR (qPCR), we examined scleral mRNA levels in recovering, plus-lens treated, and untreated control eyes for 55 candidate genes whose protein products included signaling molecules, metallopeptidases (MPs) and their inhibitors (tissue inhibitors of metallopeptidases [TIMPs]), and extracellular matrix proteins. Results: No refractive recovery was measured in the REC-2h group. The scleral mRNA expression pattern for recovering versus untreated control eyes after 2 h of recovery was similar to that found for the group (REC-0) that had no recovery time. Many genes in both groups still had downregulated expression in the treated eyes versus the control eyes. The REC-1d group showed little refractive recovery (0.1 ± 0.1 D, mean ± standard error of the mean [SEM]), and the mRNA expression pattern was similar to that of the REC-2h group, but had fewer statistically significantly downregulated genes in the recovering eyes. The REC-4d group recovered refractively by 2.6 ± 0.4 D, and displayed a "STOP" gene expression signature of mostly upregulated mRNA expression in the recovering eyes compared with the untreated control eyes. The PLW-0 (normal) group and the PLW-2h group showed no statistically significant differential gene expression. The PLW-1d group showed a small hyperopic shift (0.1 ± 0.2 D). Two genes were differentially expressed: NPR3 was upregulated in the plus lens-wearing eyes, and IGF1 was downregulated. The PLW-4d group showed a similar hyperopic shift (0.3 ± 0.4 D), confirming that the plus lens-induced 5 D of myopia produced little refractive change. In the sclera, there was an IGNORE pattern of general differential upregulation of genes in the treated eyes (22 upregulated, one downregulated) that was distinct from the STOP signature found in recovery. Ten genes were upregulated in the REC-4d group and the PLW-4d group. However, ten other genes were differentially expressed in recovery, but not in plus-lens wear, while 12 genes were differentially expressed in plus-lens wear but not in recovery. Conclusions: One day of recovery is not long enough for the emmetropization mechanism to produce significant gene expression changes in the sclera or refractive recovery. After 4 days, recovery and plus-lens wear produced altered scleral gene expression, but the patterns ("signatures") differed as to which genes showed altered expression, and whether the gene expression was up- or downregulated. Thus, myopia produced altered scleral mRNA expression in recovery and plus-lens wear, confirming that signals initiated by the retina reached the sclera, but the sclera in the elongated recovering eye responded differently from a normal sclera. This might have occurred because the recovering-eye sclera had remodeled during minus-lens compensation, making the sclera respond differently to the signals initiated by the retina. However, the myopia-produced retinal signals in plus lens-wearing animals also may have differed from those in the recovering eyes by the time the signals passed through the RPE and choroid to reach the sclera.

Sutureless transconjunctival intrascleral intraocular lens fixation: the modified Yamane technique.

PURPOSE: To evaluate the efficacy and safety of the modified Yamane technique with sutureless transconjunctival intrascleral intraocular lens fixation. METHODS: Sutureless transconjunctival intrascleral haptic fixated intraocular lens implantation was performed in patients with aphakia and dislocated intraocular lenses. A clear corneal incision (2.8 mm) was made into the temporal quadrant and a three-piece intraocular lens was implanted into the anterior chamber. The haptics of the intraocular lens were externalized with a 27 G needle via transconjunctival scleral tunnels at the 6 and 12 o'clock positions. The transconjunctival scleral tunnels were prepared to conform to the haptic position and curvature. The site of the scleral tunnels was 2mm from the limbus with a length of 2 mm in the sclera and was aimed at the end of the posterior chamber. The tips of the haptics were cauterized to create a terminal knob. The haptics were pushed back and the knobs were implanted into the scleral tunnels. RESULTS: The study cohort included 21 patients with unilateral aphakia and dislocated intraocular lenses. All patients were examined postoperatively and at postoperative day 1, day 7, month 1, and month 3. All examinations revealed formation of the anterior chamber and well-centralized intraocular lenses. No haptic-related complications of exposure, foreign body sensation, or discomfort were observed. CONCLUSION: Sutureless transconjunctival intrascleral haptic fixated intraocular lensimplantation is an effective, safe, and practical surgical alternative. This technique was superior to the Yamane method with regard to comfort and surgical duration. Further studies with longer follow-up evaluations are warranted to verify long-term complications.

Determination of iris thickness development in children using swept-source anterior-segment optical coherence tomography.

PURPOSE: The uvea comprises the iris, ciliary body, and choroid. However, the development of the anterior part (iris and ciliary body) in children is not yet fully elucidated. We investigated the iris thickness (IT) in children using swept-source anterior-segment optical coherence tomography (ASOCT). METHODS: In this retrospective, clinic-based study, we enrolled 41 children (mean ± standard deviation: 6.8 ± 3.3 years; range: 3-16; 17 males) with normal or mild refractive error. Horizontal scanning images of swept-source ASOCT were analyzed in temporal and nasal angle areas. The ITs at 1 and 2 mm from the pupil edge were measured using swept-source ASOCT. The association between IT and age, sex, and ocular morphological parameters (i.e., axial length, average corneal curvature, central corneal thickness, inter-scleral spur distance, and anterior chamber depth) was assessed using Pearson's correlation coefficient (r) and linear regression analysis. RESULTS: The average IT (temporal and nasal) at 1 and 2 mm were 0.432 ± 0.060 (0.302-0.569 mm) and 0.337 ± 0.045 (0.229-0.414 mm), respectively. There was a significant correlation between age and average IT (r = 0.45, P = 0.002 at 1 mm and r = 0.31, P = 0.042 at 2 mm). Multiple linear regression analysis revealed that age (coefficient: 0.01), axial length (-0.02), average corneal curvature (0.01), and anterior chamber depth (0.01) at 1 mm as well as age (0.00), average corneal curvature (0.09), anterior chamber depth (0.06), and male (-0.02) at 2 mm were identified as predictors of IT. CONCLUSIONS: IT in children increases with age. Additionally, IT was thinner with longer axial length and in males, thicker in eyes with deeper anterior chamber and flatter corneal curvature. Our study may partly explain the development of eyeball structures in children.

Practitioner Learning Curve in Fitting Scleral Lenses in Irregular and Regular Corneas Using a Fitting Trial.

PURPOSE: To assess the learning curve of a novel practitioner with minor previous experience with scleral lenses (SL) fitting in the initial 156 consecutive fittings in irregular and regular corneas using a fitting trial. METHODS: Prospective dispensing case series involving a total of 85 subjects (156 eyes), 122 eyes with irregular corneas (IC Group) and 34 eyes with regular corneas (RC Group). All lenses were fitted by the same practitioner with minimal previous knowledge and practice on SL fitting. The first 156 consecutive fits were studied to estimate the number of trial lenses required to achieve the optimal fit and the number of reorders required. The results were divided into 8 chronological groups of 20 fittings (eyes) each. RESULTS: There was a decrease in the number of trial lenses required to achieve the optimal fit from 2.35±0.18 lenses in the first 20 fittings to 1.56±0.13 in the last fittings (p<0.05, Wilcoxon). There were no statistically significant differences between IC and RC groups. Regarding the number of reorders, there was also a decrease from 0.95±0.17 in the first fittings to 0.25±0.11 in the last fittings (p<0.05, Wilcoxon). Thought not statistically significant, there was an increase in the use of toric designs with increasing experience. CONCLUSIONS: Practitioner fitting experience reduced both the number of trial lenses required to achieve the best fit and the number of reorders with time. After the first 60 cases, there was a significant reduction in the trial lenses and reorders necessity.