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Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma.

ABSTRACT: Purpose:Glycosaminoglycans (GAGs) are important components of the corneal stroma, and their spatiotemporal arrangement regulates the organization of collagen fibrils and maintains corneal transparency. This study was undertaken to determine the consequences of hyaluronidase (HAse) injected into the corneal stroma on stromal stiffness and ultrastructure. Methods:Equal volumes of HAse or balanced salt solution (vehicle) were injected intrastromally into the corneas of New Zealand white rabbits. Ophthalmic examination and multimodal imaging techniques, including Fourier-domain optical coherence tomography and in vivo confocal microscopy (IVCM), were performed at multiple time points to evaluate the impact of HAse treatment in vivo. Atomic force microscopy and transmission electron microscopy (TEM) were used to measure corneal stiffness and collagen's interfibrillar spacing, respectively. Results:Central corneal thickness progressively decreased after HAse injection, reaching its lowest value at day 7, and then returned to normal by day 42. The HAse did not impact the corneal endothelium but transiently altered keratocyte morphology at days 1 and 7, as measured by IVCM. HAse-injected corneas became stiffer by day 1 postinjection, were stiffest at day 7, and returned to preinjection values by day 90. Changes in stromal stiffness correlated with decreased interfibrillar spacing as measured by TEM. Conclusions:Degradation of GAGs by HAse decreases the corneal thickness and increases stromal stiffness through increased packing of the collagen fibrils in a time-dependent manner. Translational Relevance:Intrastromal HAse injection appears relatively safe in the normal cornea, but its impact on corneal biomechanics and structure under pathologic conditions requires further study.

SUBMITTER: Kim S

PROVIDER: S-EPMC7409307 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma.

Kim Soohyun S Jalilian Iman I Thomasy Sara M SM Bowman Morgan A W MAW Raghunathan Vijay Krishna VK Song Yeonju Y Reinhart-King Cynthia A CA Murphy Christopher J CJ

Translational vision science & technology 20200521 6

<h4>Purpose</h4>Glycosaminoglycans (GAGs) are important components of the corneal stroma, and their spatiotemporal arrangement regulates the organization of collagen fibrils and maintains corneal transparency. This study was undertaken to determine the consequences of hyaluronidase (HAse) injected into the corneal stroma on stromal stiffness and ultrastructure.<h4>Methods</h4>Equal volumes of HAse or balanced salt solution (vehicle) were injected intrastromally into the corneas of New Zealand wh ...[more]

PMID: 32821518

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Project description:PurposeTo evaluate the association between symptoms and signs of dry eye diseases (DED) with corneal biomechanical parameters.MethodsThis cross-sectional study enrolled 81 participants without history of ocular hypertension, glaucoma, keratoconus, corneal edema, contact lens use, diabetes, and ocular surgery. All participants were evaluated for symptoms and signs of DED using OSDI questionnaire, tear film break-up time (TBUT), conjunctival and corneal staining (NEI grading) and Schirmer test. Corneal biomechanical parameters were obtained using Corvis ST. Mixed-effects linear regression analysis was used to determine the association between symptoms and signs of DED with corneal biomechanical parameters. Difference in corneal biomechanical parameter between participants with low (Schirmer value ≤10 mm; LT group) and normal (Schirmer value >10mm; NT group) tear production was analyzed using ANCOVA test.ResultsThe median OSDI scores, TBUT, conjunctival and corneal staining scores as well as Schirmer test were 13±16.5 (range; 0-77), 5.3±4.2 seconds (range; 1.3-11), 0±1 (range; 0-4), 0±2 (ranges; 0-9) and 16±14 mm (range; 0-45) respectively. Regression analysis adjusted with participants' refraction, intraocular pressure, and central corneal thickness showed that OSDI had a negative association with highest concavity radius (P = 0.02). The association between DED signs and corneal biomechanical parameters were found between conjunctival staining scores with second applanation velocity (A2V, P = 0.04), corneal staining scores with second applanation length (A2L, P = 0.01), Schirmer test with first applanation time (A1T, P = 0.04) and first applanation velocity (P = 0.01). In subgroup analysis, there was no difference in corneal biomechanical parameters between participants with low and normal tear production (P>0.05). The associations were found between OSDI with time to highest concavity (P<0.01) and highest displacement of corneal apex (HC-DA, P = 0.04), conjunctival staining scores with A2L (P = 0.01) and A2V (P<0.01) in LT group, and Schirmer test with A1T (P = 0.02) and HC-DA (P = 0.03), corneal staining scores with A2L (P<0.01) in NT group.ConclusionsAccording to in vivo observation with Corvis ST, patients with DED showed more compliant corneas. The increase in dry eye severity was associated with the worsening of corneal biomechanics in both patients with low and normal tear production.

Project description:PURPOSE:To determine if there is a benefit to adjuvant intrastromal voriconazole (ISV) injections for primary treatment of filamentous fungal keratitis. DESIGN:Outcome-masked, randomized controlled clinical trial. PARTICIPANTS:Patients with moderate vision loss resulting from a smear-positive fungal ulcer. METHODS:Study eyes were randomized to topical natamycin plus ISV injection versus topical natamycin alone. MAIN OUTCOME MEASURES:The primary outcome of the trial was microbiological cure on 3-day repeat culture analysis. Secondary outcomes included microbiological cure on 7-day repeat culture analysis; 3-week and 3-month best spectacle-corrected visual acuity; infiltrate or scar size or both; rate of perforation; therapeutic penetrating keratoplasty (TPK); and other adverse events. RESULTS:A total of 151 patients with smear-positive ulcers were screened and 70 were enrolled at Aravind Eye Hospital, Pondicherry, India. Baseline cultures grew Fusarium in 19 samples (27%), Aspergillus in 17 samples (24%), and other filamentous fungi in 19 samples (27%) and showed negative results in 13 samples (19%). Those randomized to ISV injection had 1.82 times the odds of 3-day culture positivity after controlling for baseline culture status (95% confidence interval [CI], 0.65-5.23; P = 0.26, bias-corrected logistic regression) and 1.98 times the odds of positive 7-day culture results, after controlling for baseline culture status (95% CI, 0.69-5.91; P = 0.20, bias-corrected logistic regression). Those randomized to ISV injection showed 0.5 logMAR lines (approximately 0.5 Snellen lines) of decreased visual acuity (95% CI, -2.6 to 3.6 lines; P = 0.75) and 0.55 mm worse infiltrate or scar size or both at 3 months after controlling for baseline values (95% CI, -0.13 to 1.25; P = 0.11). Intrastromal voriconazole injections showed a 2.85-fold increased hazard of perforation after controlling for baseline infiltrate depth (95% CI, 0.76-10.75; P = 0.12) but no difference in the rate of TPK (hazard ratio, 0.95; 95% CI, 0.44-2.04; P = 0.90). CONCLUSIONS:There seems to be no benefit to adding ISV injections to topical natamycin in the primary treatment of moderate to severe filamentous fungal ulcers. Studies consistently suggest that voriconazole has a limited role in the treatment of filamentous fungal ulcers.

Project description:SIGNIFICANCE:Measured corneal biomechanical properties are driven by intraocular pressure, tissue thickness, and inherent material properties. We demonstrate tissue thickness as an important factor in the measurement of corneal biomechanics that can confound short-term effects due to UV riboflavin cross-linking (CXL) treatment. PURPOSE:We isolate the effects of tissue thickness on the measured corneal biomechanical properties using optical coherence elastography by experimentally altering the tissue hydration state and stiffness. METHODS:Dynamic optical coherence elastography was performed using phase-sensitive optical coherence tomography imaging to quantify the tissue deformation dynamics resulting from a spatially discrete, low-force air pulse (150-?m spot size; 0.8-millisecond duration; <10 Pa [<0.08 mmHg]). The time-dependent surface deformation is characterized by a viscoelastic tissue recovery response, quantified by an exponential decay constant-relaxation rate. Ex vivo rabbit globes (n = 10) with fixed intraocular pressure (15 mmHg) were topically instilled every 5 minutes with 0.9% saline for 60 minutes and 20% dextran for another 60 minutes. Measurements were made after every 20 minutes to determine the central corneal thickness (CCT) and the relaxation rates. Cross-linking treatment was performed on another 13 eyes, applying isotonic riboflavin (n = 6) and hypertonic riboflavin (n = 7) every 5 minutes for 30 minutes, followed by UV irradiation (365 nm, 3 mW/cm) for 30 minutes while instilling riboflavin. Central corneal thickness and relaxation rates were obtained before and after CXL treatment. RESULTS:Corneal thickness was positively correlated (R = 0.9) with relaxation rates. In the CXL-treated eyes, isotonic riboflavin did not affect CCT and showed a significant increase in relaxation rates (+10%; P = .01) from 2.29 ms to 2.53 ms. Hypertonic riboflavin showed a significant CCT decrease (-31%; P = .01) from 618 ?m to 429 ?m but showed little change in relaxation rates after CXL treatment. CONCLUSIONS:Corneal thickness and stiffness are correlated positively. A higher relaxation rate implied stiffer material properties after isotonic CXL treatment. Hypertonic CXL treatment results in a stiffness decrease that offsets the stiffness increase with CXL treatment.

Dataset Information

Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma.

Publications

Intrastromal Injection of Hyaluronidase Alters the Structural and Biomechanical Properties of the Corneal Stroma.

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