Dual-energy CT imaging of orbits during episcleral brachytherapy with Ru-106 plaques: A phantom study on its potential for plaque position verification.

PURPOSE: To investigate the potential of dual energy CT (DECT) to suppress metal artifacts and accurately depict episcleral brachytherapy Ru-106 plaques after surgical placement. METHODS: An anthropomorphic phantom simulating the adult head after surgical placement of a Ru-106 plaque was employed. Nine DECT acquisition protocols for orbital imaging were applied. Monochromatic 140 keV images were generated using iterative reconstruction and an available metal artifact reduction algorithm. Generated image datasets were graded by four observers regarding the ability to accurate demarcate the Ru-106 plaque. Objective image quality and visual grading analysis (VGA) was performed to compare different acquisition protocols. The DECT imaging protocol which allowed accurate plaque demarcation at minimum exposure was identified. The eye-lens dose from orbital DECT, with and without the use of radioprotective bismuth eye-shields, was determined using Monte Carlo methods. RESULTS: All DECT acquisition protocols were judged to allow clear demarcation of the plaque borders despite some moderate streaking/shading artifacts. The differences between mean observers' VGA scores for the 9 DECT imaging protocols were not statistically significant (p > 0.05). The eye-lens dose from the proposed low-exposure DECT protocol was found to be 20.1 and 22.8 mGy for the treated and the healthy eye, respectively. Bismuth shielding was found to accomplish >40% reduction in eye-lens dose without inducing shielding-related artifacts that obscure plaque delineation. CONCLUSIONS: DECT imaging of orbits after Ru-106 plaque positioning for ocular brachytherapy was found to allow artifact-free delineation of plaque margins at relatively low patient exposure, providing the potential for post-surgery plaque position verification.

Augmented Subscleral Trabeculectomy With Beta Radiation and Mitomycin C in Egyptian Glaucoma Patients.

PURPOSE: Subscleral trabeculectomy is the most common surgical treatment for glaucoma. However, wound healing and scar formation may result in bleb fibrosis, leading to bleb failure. The healing response of the wound is reported to be the single most important risk factor in determining the final intraocular pressure (IOP) after glaucoma filtration surgery. Thus, we aimed to evaluate the effect of preoperative beta irradiation and intraoperative mitomycin C (MMC) treatment as combined adjuncts to subscleral trabeculectomy in the management of glaucoma in Egyptian patients. PATIENTS AND METHODS: This prospective, interventional, comparative masked clinical study was performed between October 2016 and January 2018. This study included 50 subjects, 25 of whom underwent trabeculectomy augmented by MMC intraoperatively and beta radiation preoperatively at the bleb area (patient group #1). The remaining 25 subjects underwent trabeculectomy with MMC alone (control group #2). Beta radiation was administered 5 to 7 days before the surgery as a single dose (1000 cGy) using a strontium-90 probe. MMC (0.2 mg/mL) was administered for 2 minutes. RESULTS: There was a statistically significant difference in postoperative IOP between the groups from the second week. Intraoperative hyphema occurred in 6 cases in the control group #2, whereas no intraoperative hyphema was observed in patient group #1; this difference was statistically significant. CONCLUSIONS: Subscleral trabeculectomy augmented by beta radiation and MMC gives greater control over IOP. Therefore, we recommend using beta radiation before trabeculectomy in patients who may have a high risk of developing conjunctival fibrosis.

Argon laser-assisted hypotony model in the rabbit.

To investigate whether ocular hypotony formation with 360 degrees endocyclophotocoagulation is possible. Twelve male New Zealand White rabbits were used. Entire ciliary body epithelium was destructed with green laser photocoagulation after pars plana lensectomy and anterior vitrectomy in six rabbits. Endocyclophotocoagulation was not performed to the remaining six rabbits (control group). Intraocular pressure (IOP) was measured preoperatively and followed up everyday in the first week and weekly until the end of month one. All of the rabbits were sacrificed and ciliary bodies were left for gross and light microscopic examination. Mean baseline IOPs were similar in laser and non-laser group (14.8 ± 1.4 (range 12.2-17.3) vs 14.4 ± 1.4 (range 12.2-15.9), p = 0.650). Mean IOP was 6.6 ± 0.45 mmHg (range 5.9-7.1) in the laser group and 11.5 ± 1.2 mmHg (range 10.2-13.4) in the non-laser group in postoperative day 1. IOP was below 4 mmHg in all eyes on the second day and after in laser group. In the macroscopic evaluation, the entire ciliary body had a white (loss of pigmentation) and atrophic appearance in all of the eyes in the laser-treated group compared to non-laser group. In the laser group, light microscopic examination demonstrated a severe 360 degrees disruption of ciliary processes. Ciliary processes were covered with fibrin exudation consisting of fibroblasts. There was a mild inflammation with disruption or atrophy of ciliary body epithelium with cystic vacuolar degeneration. Three hundred sixty degrees endocyclophotocoagulation yielded severe ciliary epithelium damage. IOP reduction started very early and continued in hypotonic levels during follow up period.

Accuracy of scleral transillumination techniques to identify infant ciliary body for sclerostomy and intravitreal injections.

IMPORTANCE: There is variation in the literature for sclerotomy and intravitreal injection placement in young children, ranging from 0.5 to 3.0 mm from the limbus. We assess the accuracy of scleral transillumination to identify the ciliary body in infants for safe sclerotomy and intravitreal injections in young children. BACKGROUND: The study compares the perilimbal "dark band" seen on scleral transillumination (STI) with the ultrasound biomicroscopy (UBM), and compares these measurements with the current guidelines for sclerotomy in infants. DESIGN: Prospective case series in a tertiary paediatric hospital. PARTICIPANTS: Children aged ≤36 months undergoing general anaesthesia for eye procedures. METHODS: Scleral transillumination was performed to measure the perilimbal dark band. UBM of the ciliary body region was then performed, and correlated with transillumination findings. MAIN OUTCOME MEASURES: The midpoints of STI and UBM were compared to current cadaver-based guidelines to assess the safe point for sclerotomy. RESULTS: Twenty children were recruited, 36 STI and 35 UBM measurements were obtained. The posterior edge of the dark band had good correlation with the posterior border of the ciliary body. Transillumination and UBM correlated well for midpoint measurements. The midpoint of the dark band on transillumination was confirmed to be in the ciliary body by UBM in all cases. CONCLUSIONS AND RELEVANCE: The STI technique is a useful and fast technique to demonstrate the ciliary body. The midpoint of the dark band on STI correlates well with the UBM, and has a potential use for confirming safe-entry into the posterior segment if using current guidelines. The current cadaver-based paediatric guidelines safely avoid retinal injury.

Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of Bevacizumab, Ranibizumab and Aflibercept through Human Sclera.

PURPOSE: Permeation studies, with near infrared (NIR) light and anti-aggregation antibody formulation, were used to investigate the in vitro permeation of bevacizumab, ranibizumab and aflibercept through human sclera. METHODS: A vertical, spherical Franz cell diffusion apparatus was used for this scleral tissue permeation model. A photokinetic ocular drug delivery (PODD) testing device accommodated the placement of NIR LEDs above the donor chambers. An adjustable LED driver/square wave generator provided electrical energy with a variable pulse rate and pulse width modulation (duty cycle). RESULTS: Exposure to non-thermal NIR light had no effect on mAbs with regard to monomer concentration or antibody binding potential, as determined by SE-HPLC and ELISA. The optimal LED wavelength was found to be 950 nm. Duty cycle power of 5% vs 20% showed no difference in permeation. When compared to controls, the combination of non-aggregating antibody formulation and NIR illumination provided an average transscleral drug flux enhancement factor of 3X. CONCLUSION: Narrow wavelength incoherent (non-laser) light from an NIR LED source is not harmful to mAbs and can be used to enhance drug permeation through scleral tissue. The topical formulation, combined with pulsed NIR light irradiation, significantly improved scleral permeation of three anti-VEGF antibody drugs.

Scleral Thinning Documented by Ultrasound Biomicroscopy after Plaque Therapy for Anterior Ciliary Melanoma.

PURPOSE: To evaluate, by ultrasound biomicroscopy (UBM), changes in scleral thickness after ruthenium-106 CCB and CCC plaque (Eckert & Ziegler BE-BIG GmbH, Berlin, Germany) therapy for anterior ciliary melanoma. METHODS: Eleven patients with anterior ciliary melanoma underwent ruthenium-106 CCB and CCC plaque radiation with a radiation dose at the tumor apex of 80-100 Gy. UBM measurements performed prior to and after treatment were as follows: the largest prominence of the tumor perpendicular to the sclera and scleral thickness at scleral spur, 1.0 mm, and 2.0 mm posteriorly. RESULTS: The article presents one year follow-up results for each of the 11 patients. The mean regression of the tumor of 24.3±9.31% was observed. The thinning of the sclera was statistically significant at the scleral spur (t=1.80, p ≤ 0.05) and at maximal tumor thickness (t=1.35, P=0.05). CONCLUSION: UBM documented significant thinning of the sclera at the scleral spur and overlying the maximal tumor thickness after Ru-106 CCB and CCC plaque radiation. Taking into consideration the shortcomings of the study-small sample size, insufficient probe resolution, and subjectively determined anatomic landmarks-observed minimal thickness change of the sclera does not necessarily mean its necrosis. However, thinning of the sclera documented at one year follow-up associated with very slow regression of the tumor indicates the need for the introduction of the CIA plaque treatment in our patients with anterior ciliary melanoma.

Riboflavin and ultraviolet A irradiation for the prevention of progressive myopia in a guinea pig model.

In this study, we evaluated the effect of oral administration of riboflavin combined with whole-body ultraviolet A (UVA) irradiation on the biochemical and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Experimental groups were administered 0.1% riboflavin solution with or without vitamin C by gavage from 3 days before myopic modeling and during the modeling process. Guinea pigs underwent 30 min of whole-body UVA irradiation after each gavage for 2 weeks. For control groups, guinea pigs were administered vitamin C and underwent either whole-body UVA irradiation without 0.1% riboflavin solution or whole-body fluorescent lamp irradiation with or without 0.1% riboflavin solution. Resultantly, myopia models were established with an increased axial length and myopic diopter. Compared with myopic eyes in the control groups, the net increase in axial length, diopter and strain assessment decreased significantly, and the net decrease in sclera thickness, ultimate load, and stress assessment decreased significantly in experimental groups. MMP-2 expression showed a lower net increase, while TIMP-2 expression showed a lower net decrease. In addition, hyperplasia of scleral fibroblasts was more active in myopic eyes of experimental groups. Overall, our results showed that oral administration of riboflavin with whole-body UVA irradiation could increase the strength and stiffness of sclera by altering the biochemical and biomechanical properties, and decreases in axial elongation and myopic diopter are greater in the guinea pig myopic model.

Scleral Cross-Linking Using Riboflavin UVA Irradiation for the Prevention of Myopia Progression in a Guinea Pig Model: Blocked Axial Extension and Altered Scleral Microstructure.

PURPOSE: To develop methods of collagen cross-linking (CXL) in the sclera for the treatment of progressive myopia and to investigate the biomechanical and histological changes that occur in as a result. METHODS: Twenty 14-day-old guinea pigs were divided into 3 groups: the cross-linking group (CL, n = 8), non cross-linking group (NCL, n = 8), and control group (n = 4). The scleras of the right eyes of the guinea pigs in the CL group were surgically exposed and riboflavin was dropped onto the irradiation zone for 20 seconds prior to ultraviolet-A (UVA) irradiation. The same procedure was conducted on the NCL group but without UVA irradiation. No procedure was conducted on the control group. The right eyes of the guinea pigs in the CL and NCL groups were then fitted with -10.00DS optics for six weeks. Retinoscopy and the axial lengths (AXL) were measured at baseline, and at the second, fourth and sixth weeks post-treatment in all three groups. All animal subjects were euthanized after the sixth week and then biomechanical and histopathological examinations of the scleras were conducted. RESULTS: The mean AXL of the NCL group was longer than both the control and CL groups at six weeks (P = 0.001). The mean refractive error in the NCL group was statistically significantly more negative than both the control and the CL groups at six weeks (P = 0.001). The scleral collagen fiber arrangements of the CL and control groups were denser and more regularly distributed than the NCL group. Ultimate stress of the sclera was lowest in the NCL group, followed by the CL then the control group (P<0.05). Ultimate strain (%) of the sclera was lowest in the CL group followed by the NCL and then the control group (P<0.05). CONCLUSION: Our study demonstrates that scleral CXL using riboflavin UVA irradiation effectively prevents the progression of myopia by increasing scleral biomechanical strength in a guinea pig model.

Vision Loss Following Episcleral Brachytherapy for Uveal Melanoma: Development of a Vision Prognostication Tool.

IMPORTANCE: Vision loss following episcleral brachytherapy for uveal melanoma is difficult to predict for individual patients. OBJECTIVE: To generate a risk calculator for vision loss following episcleral brachytherapy for uveal melanoma. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of data was conducted at a multispecialty tertiary care center in Cleveland, Ohio. All patients with primary ciliary body or choroidal melanoma treated with iodine 125 or ruthenium 106 episcleral brachytherapy between January 1, 2004, and December 30, 2013, were included. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log-rank analyses) were used to estimate freedom from vision loss. Bootstrap resampling was performed to bias correct this estimate. MAIN OUTCOMES AND MEASURES: Vision loss (to visual acuity [VA] worse than 20/50 and worse than 20/200). RESULTS: A total of 311 patients were included in the study, with a mean (SD) age of 62 (14.7) years at start of treatment and a median follow-up of 36 months (interquartile range, 18-60 months). At presentation, VA was better than or equal to 20/50 in 199 patients (64%) and better than or equal to 20/200 in 289 patients (93%). By Kaplan-Meier analysis, VA less than 20/200 at 3 years was not associated with sex, diabetes, systemic hypertension, or hypercholesterolemia but was associated with history of ocular comorbidities, type of isotope (ruthenium 106 or iodine 125), and initial VA ( >20/50 or <20/50). By multivariable analysis, age (hazard ratio [HR], 0.97; 95% CI, 0.94-1.00; P = .06), largest basal diameter (HR, 1.25; 95% CI, 1.16-1.34; P = <.001), total radiation dose to the fovea (HR, 1.03; 95% CI, 1.01-1.04; P = .001) and optic disc (HR, 1.01; 95% CI, 1.00-1.01; P = .005), and initial VA worse than 20/50 (HR, 1.85; 95% CI, 1.20-2.85; P = .005) were predictive of vision loss to a VA of less than 20/200. The concordance index for the full data set was 0.77. Using these data, an online risk calculator was developed to predict vision loss following episcleral brachytherapy. CONCLUSIONS AND RELEVANCE: The vision prognostication tool presented herein needs to be validated by independent data sets. This tool may improve counseling for patients being evaluated for episcleral brachytherapy. At-risk individuals identified by this tool could be considered for inclusion into trials exploring prevention or treatment of radiation retinopathy and alternative therapies of uveal melanoma.

Corneal Patch Graft: A New Approach for Scleral Necrosis Secondary to Plaque Radiotherapy.

PURPOSE: To evaluate the anatomical outcomes of corneal patch grafts in patients with progressive scleral necrosis secondary to plaque radiotherapy used for uveal malignant melanoma management. METHODS: In this case series, 4 patients with progressive scleral necrosis after Ru-106 plaque radiotherapy underwent corneal patch grafts with the anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue to strengthen the sclera and to improve appearance of the eye. RESULTS: Ciliary body involvement was evident in all cases. All 4 patients had received radiation doses of 400 Gy or more to the tumor base. The mean time interval between plaque radiotherapy and scleral necrosis was 24.5 ± 7.5 months (range, 18-34 months). Successful results were achieved in all patients with tectonic graft. No patients experienced graft thinning, rejection, infection, or tumor recurrence in a mean follow-up of 28.5 ± 7.9 months (range, 20-39 months). CONCLUSIONS: Corneal patch graft by anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue results in successful restoration of globe integrity and satisfactory cosmetic appearance in patients with scleral necrosis secondary to plaque radiotherapy.

Puerarin, an isoflavone compound extracted from Gegen (Radix Puerariae Lobatae), modulates sclera remodeling caused by extremely low frequency electromagnetic fields.

OBJECTIVE: To evaluate the protective effect of puerarin [an isoflavone compound extracted from Gegen (Radix Puerariae Lobatae)] in scleral remodeling induced by extremely low frequency electromagnetic fields (ELF-EMFs). METHODS: Human fetal scleral fibroblasts (HFSFs) were divided into 5 groups: (a) untreated controls; (b) cells treated with ELF-EMFs; (c) cells treated with ELF-EMFs and puerarin 0.1 µM; (d) cells treated with ELF-EMFs and puerarin 1 µM; (e) cells treated with ELF-EMFs and puerarin 10 µM. Cell proliferation activity was measured by the cell-counting kit-8 assay. Matrix metalloproteinase-2 (MMP-2) activity was measured by gelatin enzymography. MMP-2 and collagenⅠ(COL1A1) mRNA, protein expression were measured by Real-Time polymerase chain reaction , Western blot analysis, respectively. RESULTS: Puerarin reduced the inhibition in cell proliferation, MMP-2 activity, mRNA, protein expression of HFSFs exposed to ELF-EMFs and enhanced the COL1A1 mRNA and protein expression. CONCLUSION: Puerarin was found to participate in the matrix remodeling process. It might be a potential agent for the treatment of extracellular matrix degradation of sclera associated with ocular conditions.

Use of the Toric Surgical Marker to Aid in Intraoperative Plaque Placement for the USC Eye Physics Plaques to Treat Uveal Melanoma: A New Surgical Technique.

BACKGROUND AND OBJECTIVE: To describe a new surgical technique for intraoperative placement of Eye Physics (EP) plaques for uveal melanoma using a toric marker. PATIENTS AND METHODS: A toric marker is designed for cataract surgery to align the axis of astigmatism; its use was modified in this protocol to mark the axis of suture coordinates as calculated by Plaque Simulator (PS) software. RESULTS: The toric marker can be used to localize suture coordinates, in degrees, during intraoperative plaque placement. Linear marking using the toric marker decreases potential inaccuracies associated with the surgeon estimating 'clock-hours' by dot placement. CONCLUSION: Use of the toric marker aided surgical placement of EP plaques. The EP planning protocol is now designed to display the suture coordinates either by clock-hours or degrees, per surgeon preference. Future research is necessary to determine whether routine use of the toric marker improves operative efficiency. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:866-870.].

Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application.

Several scleral cross-linking (SXL) methods were suggested to increase the biomechanical stiffness of scleral tissue and therefore, to inhibit axial eye elongation in progressive myopia. In addition to scleral cross-linking and biomechanical effects caused by riboflavin and light irradiation such a treatment might induce tissue damage, dependent on the light intensity used. Therefore, we characterized the damage threshold and mechanical stiffening effect in rabbit eyes after application of riboflavin combined with various blue light intensities. Adult pigmented and albino rabbits were treated with riboflavin (0.5 %) and varying blue light (450 ± 50 nm) dosages from 18 to 780 J/cm(2) (15 to 650 mW/cm(2) for 20 min). Scleral, choroidal and retinal tissue alterations were detected by means of light microscopy, electron microscopy and immunohistochemistry. Biomechanical changes were measured by shear rheology. Blue light dosages of 480 J/cm(2) (400 mW/cm(2)) and beyond induced pathological changes in ocular tissues; the damage threshold was defined by the light intensities which induced cellular degeneration and/or massive collagen structure changes. At such high dosages, we observed alterations of the collagen structure in scleral tissue, as well as pigment aggregation, internal hemorrhages, and collapsed blood vessels. Additionally, photoreceptor degenerations associated with microglia activation and macroglia cell reactivity in the retina were detected. These pathological alterations were locally restricted to the treated areas. Pigmentation of rabbit eyes did not change the damage threshold after a treatment with riboflavin and blue light but seems to influence the vulnerability for blue light irradiations. Increased biomechanical stiffness of scleral tissue could be achieved with blue light intensities below the characterized damage threshold. We conclude that riboflavin and blue light application increased the biomechanical stiffness of scleral tissue at blue light energy levels below the damage threshold. Therefore, applied blue light intensities below the characterized damage threshold might define a therapeutic blue light tolerance range.

Prescribing to tumor apex in episcleral plaque iodine-125 brachytherapy for medium-sized choroidal melanoma: A single-institutional retrospective review.

PURPOSE: To report an institutional experience with episcleral plaque brachytherapy for medium-sized uveal melanoma. Variations in prescription dose point and dose rate were compared with Collaborative Ocular Melanoma Study (COMS) Group. METHODS AND MATERIALS: A retrospective review was performed for 116 patients treated with iodine-125 plaque brachytherapy. About 85 Gy was prescribed to either the tumor apex (108 patients) or at 5 mm (8 patients) with dose rate ranging from 50.6 to 98.2 cGy/h. Patients were followed up for local tumor control, eye preservation, and vision retention. Dose and dose rate to tumor and sensitive structures were calculated. Multivariate and univariate analyses were performed to investigate correlation between clinical outcomes and dose/dose rate variables. RESULTS: Patients in this study were slightly older with worse visual acuity at baseline, but tumor size and position and ratio of ciliary body involvement were comparable to COMS population. Outcomes data were comparable to COMS: 95.3% local tumor control at 5 years and 77.7% vision preservation at 3 years. Only 4 patients needed enucleation because of tumor growth. Significant correlation was found between enucleation and tumor height and maximal scleral dose/dose rate as well as vision retention and tumor height and macula dose/dose rate. CONCLUSIONS: For tumors with <5 mm height, prescribing to tumor apex enabled to decrease dose to all sensitive structures without any loss of local control. Although dose rate was lowered to 50.6 cGy/h from the American Brachytherapy Society guidelines (60-105 cGy/h) because of limited availability of operating room (i.e., weekly), there was no difference in either local tumor control or complications.

Independent dosimetric assessment of the model EP917 episcleral brachytherapy plaque.

PURPOSE: To investigate the influence of slot design on dose distributions and dose-volume histograms (DVHs) for the model EP917 plaque for episcleral brachytherapy. METHODS: Dimensions and orientations of the slots were measured for three model EP917 plaques and compared to data in the Plaque Simulator (PS) treatment planning software (version 5.7.6). These independently determined coordinates were incorporated into the MCNP Monte Carlo simulation environment to obtain dose from the plaques in a water environment and in a clinical environment with ocular structures. A tumor volume was simulated as 5 mm in apical height and 11 mm in basal diameter. Variations in plaque mass density and composition; slot length, width, and depth; seed positioning; and Ag-marker rod positioning were simulated to examine their influence on plaque central axis (CAX) and planar dose distributions, and DVHs. RESULTS: Seed shifts in a single slot toward the eye and shifts of the(125)I-coated Ag rod within the capsule had the greatest impact on CAX dose distribution. A shift of 0.0994 mm toward the eye increased dose by 14%, 9%, 4.3%, and 2.7% at 1, 2, 5, and 10 mm, respectively, from the inner sclera. When examining the fully-modeled plaque in the ocular geometry, the largest dose variations were caused by shifting the Ag rods toward the sclera and shifting the seeds away from the globe when the slots were made 0.51 mm deeper, causing +34.3% and -69.4% dose changes to the outer sclera, respectively. At points along the CAX, dose from the full plaque geometry using the measured slot design was 2.4%±1.1% higher than the manufacturer-provided slot design and 2.2%±2.3% higher than the homogeneous calculation of PS treatment planning results. The ratio of D10 values for the measured slot design to the D10 values for the manufacturer-provided slot design was higher by 9%, 10%, and 19% for the tumor, inner sclera, and outer sclera, respectively. In comparison to the measured slot design, a theoretical plaque having narrower and deeper slots delivered 30%, 37%, and 62% lower D10 doses to the tumor, inner sclera, and outer sclera, respectively. CONCLUSIONS: While the measured positions of the slots on the model EP917 plaque were in close agreement (<0.7 mm) with the PS values, small differences in the slot shape caused substantial differences in dose distributions and DVH metrics. Increasing slot depth by 0.1 mm decreased outer scleral dose by 20%, yet shifting the Ag rods in the seeds toward the globe by 0.1 mm increased outer scleral dose by 35%. The clinical medical physicist is advised to measure these types of plaques upon acceptance testing before clinical use to inspect slot shape and position for comparison with data used for treatment planning purposes.

[Morphologically reasonable application of 1.44 microm Nd:YAG laser in ocular surgery for distant hemostasis in conjunctival and episcleral vessels].

The article discusses morphological changes in bulbar conjunctiva and episclera after experimental exposure to Nd:YAG laser radiation at 1.44 pm in comparison to the effect of diathermal coagulator Mira TR4000. The results proved the use of 1.44 microm Nd:YAG laser in ocular surgery for distant hemostasis morphologically reasonable. Non-contact and directional laser treatment is more delicate as it produces smaller irradiated area. The depth of penetration and tissue heating is very limited. Neither excessive reparation, nor scarring is found in the exposed area. On the contrary, diathermy is a contact procedure associated with irregular distribution of heat, which causes large tissue burns and necrosis with subsequent adherent scar formation.

Microstructural changes in sclera under thermo-mechanical effect of 1.56 µm laser radiation increasing transscleral humor outflow.

BACKGROUND AND OBJECTIVES: Pores in the sclera are a candidate pathway for aqueous transport and therefore can be utilized to decrease the intraocular pressure (IOP) in glaucomatous eyes. Since pore formation is a well-known mechanism for stress relaxation in solids, laser-induced creation of pores in cartilage increases hydraulic permeability and promotes tissue regeneration. The aim of this paper is to demonstrate the thermo-mechanical effect of non-destructive laser irradiation on microstructural changes in sclera, in particular pore formation, resulting in substantial increase of water permeability of eye tissues that can be a novel approach to normalize the IOP. MATERIALS AND METHODS: Experiments were performed ex vivo on eight eyes of four mini-pigs and in vivo on eight eyes of four rabbits using pulse repetitive laser radiation of 1.56 µm in wavelength. Twenty laser spots of 0.6 mm in diameter with laser settings (power 0.9 W, pulse duration of 200 milliseconds, pulse repetition rate of 2 Hz) resulting in substantial increase of sclera hydraulic permeability were applied on the sclera at 1-2 mm from the eye limb. Sclera and underlying structures (choroid and ciliary body) of the rabbits' eyes were examined histologically in 1 and 45 days after laser irradiation, atomic force microscope (AFM) was applied before and after laser irradiation. RESULTS: Histological and AFM examinations have clearly recognized laser-assisted stable structural alterations: rarefication of the collagen structure in the laser irradiated zone and formation of sub-micron pores. Laser-induced alterations in the structure of ciliary bodies were small in size and mainly reversible. We have proposed a possible mechanism of the arising pores stabilization due to formation of small stable gas bubbles in sclera tissue. CONCLUSIONS: It is shown, for the first time, that thermo-mechanical effect of pulse repetitive laser irradiation results in pores formation in sclera. That can be a basis of a novel, safe, and effective technique for IOP normalization due to enhancing of uveoscleral outflow under non-destructive laser irradiation of the sclera.

Rod-like microglia are restricted to eyes with laser-induced ocular hypertension but absent from the microglial changes in the contralateral untreated eye.

In the mouse model of unilateral laser-induced ocular hypertension (OHT) the microglia in both the treated and the normotensive untreated contralateral eye have morphological signs of activation and up-regulation of MHC-II expression in comparison with naïve. In the brain, rod-like microglia align to less-injured neurons in an effort to limit damage. We investigate whether: i) microglial activation is secondary to laser injury or to a higher IOP and; ii) the presence of rod-like microglia is related to OHT. Three groups of mice were used: age-matched control (naïve, n=15); and two lasered: limbal (OHT, n=15); and non-draining portion of the sclera (scleral, n=3). In the lasered animals, treated eyes as well as contralateral eyes were analysed. Retinal whole-mounts were immunostained with antibodies against, Iba-1, NF-200, MHC-II, CD86, CD68 and Ym1. In the scleral group (normal ocular pressure) no microglial signs of activation were found. Similarly to naïve eyes, OHT-eyes and their contralateral eyes had ramified microglia in the nerve-fibre layer related to the blood vessel. However, only eyes with OHT had rod-like microglia that aligned end-to-end, coupling to form trains of multiple cells running parallel to axons in the retinal surface. Rod-like microglia were CD68+ and were related to retinal ganglion cells (RGCs) showing signs of degeneration (NF-200+RGCs). Although MHC-II expression was up-regulated in the microglia of the NFL both in OHT-eyes and their contralateral eyes, no expression of CD86 and Ym1 was detected in ramified or in rod-like microglia. After 15 days of unilateral lasering of the limbal and the non-draining portion of the sclera, activated microglia was restricted to OHT-eyes and their contralateral eyes. However, rod-like microglia were restricted to eyes with OHT and degenerated NF-200+RGCs and were absent from their contralateral eyes. Thus, rod-like microglia seem be related to the neurodegeneration associated with HTO.