Mammalian Animal and Human Retinal Organ Culture as Pre-Clinical Model to Evaluate Oxidative Stress and Antioxidant Intraocular Therapeutics.

Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in terms of transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed the model's quality, induced OS, and tested the efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3-14 d. OS was induced by a high amount of glucose or hydrogen peroxide (H2O2) and treated with scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage colony-stimulating factor (GM-CSF). The tissue morphology, cell viability, inflammation, and glutathione level were determined. The retina samples showed only moderate necrosis (23.83 ± 5.05 increased to 27.00 ± 1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3 ± 59.9 vs. 435.7 ± 166.8 nM ATP in the controls) and the antioxidants reduced OS-induced apoptosis (from 124.20 ± 51.09 to 60.80 ± 319.66 cells/image after the scutellarin treatment). Enhanced mammalian animal and human retina cultures enable reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development.

Comparison of Conventional and Femtosecond Laser-Assisted Cataract Surgery Regarding Macula Behavior and Thickness.

Background: The aim of the study was to compare macular thickness behavior and clinical outcomes after femtosecond laser-assisted cataract surgery (FLACS) versus phacoemulsification conventional surgery (PCS). Methods: Macular Optical Coherence Tomography OCT was analyzed in 42 patients preoperatively, 1 day, 12 days, 4 weeks and 6 weeks postoperatively according to the 9-field Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Clinical findings were collected in both the FLACS group and the PCS group. Results: There was no significant difference in macular thickness between the FLACS and PCS groups (p > 0.05). However, from postoperative day 12 onwards, there was a significant increase in macular thickness observed in both groups (p < 0.001). In the FLACS group, a significant increase in visual acuity was observed on the first postoperative day, as compared to the PCS group (p = 0.006). Conclusions: The use of a low-energy high-frequency femtosecond laser has potentially no effect on postoperative macular thickness. In the FLACS group, visual rehabilitation was significantly faster as compared to the PCS group. No complications occurred intraoperatively in either group.

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications-risks and mitigation.

Proliferative diabetic retinopathy (PDR) the sequel of diabetic retinopathy (DR), a frequent complication of diabetes mellitus (DM), is the leading cause of blindness in the working-age population. The current screening process for the DR risk is not sufficiently effective such that often the disease is undetected until irreversible damage occurs. Diabetes-associated small vessel disease and neuroretinal changes create a vicious cycle resulting in the conversion of DR into PDR with characteristic ocular attributes including excessive mitochondrial and retinal cell damage, chronic inflammation, neovascularisation, and reduced visual field. PDR is considered an independent predictor of other severe diabetic complications such as ischemic stroke. A "domino effect" is highly characteristic for the cascading DM complications in which DR is an early indicator of impaired molecular and visual signaling. Mitochondrial health control is clinically relevant in DR management, and multi-omic tear fluid analysis can be instrumental for DR prognosis and PDR prediction. Altered metabolic pathways and bioenergetics, microvascular deficits and small vessel disease, chronic inflammation, and excessive tissue remodelling are in focus of this article as evidence-based targets for a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary DR care management.

Bowman Layer Transplantation for Treating Keratoconus-Preliminary Findings.

(1) Background: Mid-stromal isolated Bowman layer transplantation aims to reduce and stabilize corneal ectasia in patients with advanced, progressive keratoconus. The purpose of this review is to evaluate the effectiveness and safety of this new surgical technique. (2) Methods: Following the PRISMA statement and checklist, we searched Medline, the Cochrane Controlled Trials Register, and Embase and used a broad systematic search strategy according to the Cochrane Collaboration. (3) Results: Eight studies with a total number of 120 eyes of 106 patients met our inclusion criteria. One month after Bowman layer transplantation, patients with keratoconus showed a significant decrease in the measured simulated keratometry (-4.74 D [95% CI -6.79 to -2.69]) and the maximum keratometry (-7.41 D [95% CI -9.64 to -5.19]), which remained significant one year postoperatively (-2.91 D [95% CI -5.29 to -0.53] and -5.80 D [-8.49 to -3.12]). Intra- and postoperative complications were observed in 3% and 9% of the patients, respectively. An estimated success rate of 75% to 85% was achieved by experienced surgeons at 5 to 8 years postoperatively. (4) Conclusions: Bowman layer transplantation may be an effective and safe treatment option in patients with advanced, progressive keratoconus. Additional multicenter prospective interventional studies are needed to confirm these preliminary findings.

Short communication: unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities - preliminary data for PPPM validation.

Type 2 diabetes (T2DM) defined as the adult-onset type that is primarily not insulin-dependent, comprises over 95% of all diabetes mellitus (DM) cases. According to global records, 537 million adults aged 20-79 years are affected by DM that means at least 1 out of 15 persons. This number is projected to grow by 51% by the year 2045. One of the most common complications of T2DM is diabetic retinopathy (DR) with an overall prevalence over 30%. The total number of the DR-related visual impairments is on the rise, due to the growing T2DM population. Proliferative diabetic retinopathy (PDR) is the progressing DR and leading cause of preventable blindness in working-age adults. Moreover, PDR with characteristic systemic attributes including mitochondrial impairment, increased cell death and chronic inflammation, is an independent predictor of the cascading DM-complications such as ischemic stroke. Therefore, early DR is a reliable predictor appearing upstream of this "domino effect". Global screening, leading to timely identification of DM-related complications, is insufficiently implemented by currently applied reactive medicine. A personalised predictive approach and cost-effective targeted prevention shortly - predictive, preventive and personalised medicine (PPPM / 3PM) could make a good use of the accumulated knowledge, preventing blindness and other severe DM complications. In order to reach this goal, reliable stage- and disease-specific biomarker panels are needed characterised by an easy way of the sample collection, high sensitivity and specificity of analyses. In the current study, we tested the hypothesis that non-invasively collected tear fluid is a robust source for the analysis of ocular and systemic (DM-related complications) biomarker patterns suitable for differential diagnosis of stable DR versus PDR. Here, we report the first results of the comprehensive ongoing study, in which we correlate individualised patient profiles (healthy controls versus patients with stable D as well as patients with PDR with and without co-morbidities) with their metabolic profiles in the tear fluid. Comparative mass spectrometric analysis performed has identified following metabolic clusters which are differentially expressed in the groups of comparison: acylcarnitines, amino acid & related compounds, bile acids, ceramides, lysophosphatidyl-choline, nucleobases & related compounds, phosphatidyl-cholines, triglycerides, cholesterol esters, and fatty acids. Our preliminary data strongly support potential clinical utility of metabolic patterns in the tear fluid indicating a unique metabolic signature characteristic for the DR stages and PDR progression. This pilot study creates a platform for validating the tear fluid biomarker patterns to stratify T2DM-patients predisposed to the PDR. Moreover, since PDR is an independent predictor of severe T2DM-related complications such as ischemic stroke, our international project aims to create an analytical prototype for the "diagnostic tree" (yes/no) applicable to healthrisk assessment in diabetes care.

GMP-Grade Manufacturing and Quality Control of a Non-Virally Engineered Advanced Therapy Medicinal Product for Personalized Treatment of Age-Related Macular Degeneration.

The introduction of new therapeutics requires validation of Good Manufacturing Practice (GMP)-grade manufacturing including suitable quality controls. This is challenging for Advanced Therapy Medicinal Products (ATMP) with personalized batches. We have developed a person-alized, cell-based gene therapy to treat age-related macular degeneration and established a vali-dation strategy of the GMP-grade manufacture for the ATMP; manufacturing and quality control were challenging due to a low cell number, batch-to-batch variability and short production duration. Instead of patient iris pigment epithelial cells, human donor tissue was used to produce the transfected cell product ("tIPE"). We implemented an extended validation of 104 tIPE productions. Procedure, operators and devices have been validated and qualified by determining cell number, viability, extracellular DNA, sterility, duration, temperature and volume. Transfected autologous cells were transplanted to rabbits verifying feasibility of the treatment. A container has been engineered to ensure a safe transport from the production to the surgery site. Criteria for successful validation and qualification were based on tIPE's Critical Quality Attributes and Process Parameters, its manufacture and release criteria. The validated process and qualified operators are essential to bring the ATMP into clinic and offer a general strategy for the transfer to other manufacture centers and personalized ATMPs.

Vascular risk factors for optical coherence tomography-detected macular cysts: The Maastricht Study.

PURPOSE: To investigate whether higher blood pressure and greater arterial stiffness are associated with the presence of macular cysts and whether this association is already present in the absence of micro-aneurysms in individuals with and without type 2 diabetes. METHODS: Using spectral domain optical coherence tomography (OCT), we performed a macular volume scan in 2647 individuals (mean age 60 ± 8 years, 50% men, 27% type 2 diabetes). The association between macular cysts and 24-hour systolic and diastolic blood pressure, pulse pressure, mean arterial blood pressure, carotid-femoral pulse wave velocity and carotid distensibility was assessed by use of logistic regression. RESULTS: Twenty-four hours systolic blood pressure was associated with the presence of macular cysts [OR = 1.03 (95% CI 1.00-1.05) per 1 mmHg, p = 0.03]. 24 hr pulse pressure [OR = 1.61 (95% CI 1.11-2.34) per 10 mmHg, p = 0.01] and carotid-femoral pulse wave velocity [OR = 1.16 (95% CI 1.02-1.32) per 1 m/s, p = 0.02] were associated with macular cysts, while carotid distensibility was not [OR = 1.03 (95% CI 0.96-1.11) per 1.0*10-3 /kPa, p = 0.45]. Associations were similar in individuals with and without type 2 diabetes and were already present in the absence of micro-aneurysms. CONCLUSION: Twenty-four hours systolic blood pressure, 24 hr pulse pressure and carotid-femoral pulse wave velocity are associated with the presence of OCT-detected macular cysts in individuals with and without type 2 diabetes, even in the absence of micro-aneurysms. Therefore, blood pressure and aortic stiffness are potential factors contributing to macular cysts.

Reduced corneal nerve fibre length in prediabetes and type 2 diabetes: The Maastricht Study.

PURPOSE: In individuals with diabetes, injury to the corneal nerve fibres predisposes to delayed corneal epithelial healing, reduced corneal sensitivity and corneal erosion. We investigated to what extent a reduction in corneal nerve fibre length (CNFL) is present in individuals with prediabetes or type 2 diabetes (DM2) compared with individuals with normal glucose metabolism (NGM). METHODS: Using composite images acquired by corneal confocal microscopy, we assessed total CNFL per mm2 in the subbasal nerve plexus of the cornea in 134 participants (mean age 59 ± 8 years, 49% men, 87 NGM, 20 prediabetes, 27 DM2). Multivariable linear regression was used to assess the association between CNFL and glucose metabolism status, adjusted for age and sex. RESULTS: In individuals with type 2 diabetes, the mean CNFL was significantly reduced [ß = -1.86 mm/mm2 (95% CI -3.64 to -0.08), p = 0.04], as compared with individuals with normal glucose metabolism after adjustment for age and sex. Part of the reduction was present in individuals with prediabetes [ß = -0.96 mm/mm2 (95% CI -2.91 to 0.99), p = 0.34], with a linear trend of corneal nerve fibre reduction with severity of glucose metabolism status (p trend = 0.04). CONCLUSIONS: A significant reduction in CNFL was found in individuals with DM2 compared with individuals with NGM. A trend of reduction in CNFL was observed between individuals with NGM and prediabetes. The reduction in corneal nerve fibre length could contribute to a delayed corneal healing and an increased risk for corneal complications after surgery.

Prevalence of optical coherence tomography detected vitreomacular interface disorders: The Maastricht Study.

PURPOSE: To calculate the prevalence of all vitreomacular interface (VMI) disorders and stratify according to age, sex and (pre)diabetes status. METHODS: The presence of VMI disorders was assessed in 2660 participants aged between 40 and 75 years from The Maastricht Study who had a gradable macular spectral-domain optical coherence tomography (SD-OCT) volume scan in at least one eye [mean 59.7 ± 8.2 years, 50.2% men, 1531 normal glucose metabolism (NGM), 401 prediabetes, 728 type 2 diabetes (DM2, oversampled)]. A stratified and multivariable logistic regression analysis was used. RESULTS: The prevalence of the different VMI disorders for individuals with NGM, prediabetes and DM2 was, respectively, 5.7%, 6% and 6.7% for epiretinal membranes; 6%, 9.6% and 6.8% for vitreomacular traction; 1.1%, 0.7% and 0.3% for lamellar macular holes; 0.1%, 0% and 0% for pseudoholes; 1.1%, 1.9% and 5.5% for macular cysts. None of the participants was diagnosed with a macular hole. The prevalence of epiretinal membranes, vitreomacular traction and macular cysts was higher with age (p < 0.001). Vitreomacular traction and lamellar macular holes were more frequent in women (p < 0.01). DM2 is positively associated [OR = 3.9 (95% CI 2.11-7.22, p < 0.001)] with macular cysts and negatively associated with lamellar macular holes [OR = 0.2 (95% CI 0.04-0.9, p = 0.036)] after adjustment for age and sex. The calculated prevalence of VMI disorders was 15.9%. CONCLUSIONS: The calculated prevalence of VMI disorders in individuals aged between 40 and 75 years is 15.9%. The prevalence depends on age, sex and glucose metabolism status for several types of VMI disorders.

Macular thinning in prediabetes or type 2 diabetes without diabetic retinopathy: the Maastricht Study.

PURPOSE: To assess macular thinning in individuals with prediabetes or type 2 diabetes without diabetic retinopathy (DM2 w/o DR) compared with individuals with normal glucose metabolism (NGM). METHODS: Using spectral domain optical coherence tomography (SD-OCT), we measured macular thickness in six subfields as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS) in 1838 participants from The Maastricht Study, a population-based cohort study (mean age 59 ± 8 years, 49% men, 1087 NGM, 279 prediabetes, 472 DM2 w/o DR). Multivariable linear regression was used to assess the association between macular thickness and glucose metabolism status. RESULTS: After adjustment for age, sex and spherical equivalent, individuals with prediabetes showed a significant decrease in pericentral superior macular thickness [ß = -2.14 µm (95% confidence interval (CI): -4.24 to -0.03), p < 0.05] compared with individuals with NGM. In individuals with DM2 w/o DR, the fovea [ß = -4.05 µm (95% CI: -6.30 to -1.79), p < 0.001] and the four pericentral quadrants (range: ß = -4.64 to -5.29 µm, p < 0.001) were significantly thinner compared with individuals with NGM. There was a significant linear trend of macular thinning with severity of glucose metabolism status in five subfields (p < 0.001). CONCLUSION: Macular thickness is reduced in prediabetes and a greater reduction occurs in DM2, even before DR is clinically present. About half of the thinning observed in DM2 w/o DR was already found in prediabetes. Generalized thinning of the macula could be related to thinning of the temporal side of the optic nerve head through the connecting papillo-macular bundle.

New ophthalmologic imaging techniques for detection and monitoring of neurodegenerative changes in diabetes: a systematic review.

Optical coherence tomography (OCT) of the retina and around the optic nerve head and corneal confocal microscopy (CCM) are non-invasive and repeatable techniques that can quantify ocular neurodegenerative changes in individuals with diabetes. We systematically reviewed studies of ocular neurodegenerative changes in adults with type 1 or type 2 diabetes and noted changes in the retina, the optic nerve head, and the cornea. Of the 30 studies that met our inclusion criteria, 14 used OCT and 16 used CCM to assess ocular neurodegenerative changes. Even in the absence of diabetic retinopathy, several layers in the retina and the mean retinal nerve fibre layer around the optic nerve head were significantly thinner (-5·36 µm [95% CI -7·13 to -3·58]) in individuals with type 2 diabetes compared with individuals without diabetes. In individuals with type 1 diabetes without retinopathy none of the intraretinal layer thicknesses were significantly reduced compared with individuals without diabetes. In the absence of diabetic polyneuropathy, individuals with type 2 diabetes had a lower nerve density (nerve branch density: -1·10/mm(2) [95% CI -4·22 to 2·02]), nerve fibre density: -5·80/mm(2) [-8·06 to -3·54], and nerve fibre length: -4·00 mm/mm(2) [-5·93 to -2·07]) in the subbasal nerve plexus of the cornea than individuals without diabetes. Individuals with type 1 diabetes without polyneuropathy also had a lower nerve density (nerve branch density: -7·74/mm(2) [95% CI -14·13 to -1·34], nerve fibre density: -2·68/mm(2) [-5·56 to 0·20]), and nerve fibre length: -2·58 mm/mm(2) [-3·94 to -1·21]). Ocular neurodegenerative changes are more evident when diabetic retinopathy or polyneuropathy is present. OCT and CCM are potentially useful, in addition to conventional clinical methods, to assess diabetic neurodegenerative changes. Additional research is needed to determine their incremental benefit and to standardise procedures before the application of OCT and CCM in daily practice.

Retinal oxygen metabolism in healthy subjects and glaucoma patients.

BACKGROUND: To test whether retinal oxygen metabolism is different in glaucoma patients compared with healthy subjects. METHODS: This was a two-centre study where retinal vessel oxygen saturation was measured in glaucoma patients and healthy individuals with a non-invasive spectrophotometric retinal oximeter. Visual fields were obtained in the glaucoma patients. RESULTS: No statistical difference was found in retinal oxygen saturation in arterioles (p=0.16), venules (p=0.16) and arteriovenous difference (p=0.24) when all glaucoma patients (n=74) were compared with healthy individuals (n=89). When patients with advanced glaucoma (visual field mean defect (MD ≥ 10 dB, n=21)) were compared with healthy individuals, the oxygen saturation in venules was higher in glaucoma patients (58.2% ± 5.4% vs 53.8% ± 6.4%; p=0.0054, mean ± SD) and the arteriovenous difference was lower in glaucoma patients (36.4% ± 4.7% vs 39.5% ± 5.7%; p=0.021). In glaucoma patients with mild glaucoma (visual field MD ≤ 5 dB, n=33), no statistical differences were found in retinal oxygen saturation compared with healthy individuals. CONCLUSIONS: Glaucoma patients with advanced glaucoma have higher oxygen saturation in venules and lower arteriovenous difference in oxygen saturation compared with healthy individuals. The decreased arteriovenous difference in severe glaucoma may be related to lower oxygen consumption secondary to neuropathy.

Oximetry in glaucoma: correlation of metabolic change with structural and functional damage.

PURPOSE: To determine whether retinal vessel oxygen saturation in patients with glaucoma is associated with structural optic disc and retinal nerve fibre layer (RNFL) changes and visual field (VF) defects. METHODS: Fifty-nine patients with confirmed glaucoma were recruited at University Hospitals Leuven. Retinal oxygen saturation in patients with glaucoma was measured with a noninvasive spectrophotometric retinal oximeter (Oxymap ehf, Reykjavik, Iceland). VF and Heidelberg retinal tomographies (HRTs) were performed on the same day. Statistical analysis was performed using Student's t-test and Pearson's or Spearman correlation coefficient. RESULTS: The mean oxygen saturation in venules was higher in patients with severe VF defects compared to those patients with mild VF defects (69 ± 3% versus 65 ± 6% respectively; p = 0.0003; n = 59). Accordingly, the arteriovenous (AV) difference in oxygen saturation was lower in patients with worse VF compared to those with better VF (29 ± 3% versus 33 ± 6% respectively; p = 0.002). The oxygen saturation in venules correlated with the VF mean defects (r = -0.42; p = 0.001; n = 59) as well as with the structural HRT parameters rim area and RNFL thickness (r = -0.39; p = 0.008 and r = -0.26; p = 0.05 respectively; n = 53). The AV difference decreased significantly as the VF defect worsened (r = 0.38; p = 0.003), as the rim area diminished (r = 0.29; p = 0.03) and as the RNFL thickness decreased (r = 0.27; p = 0.05). No correlation was found between the oxygen saturation in retinal arterioles and either of these parameters. CONCLUSION: Severe glaucomatous damage is associated with increased oxygen saturation in retinal venules and decreased AV difference in oxygen saturation. These data suggest that in eyes with severe glaucomatous damage, reduced retinal oxygen consumption is consistent with tissue loss.

Lack of spontaneous venous pulsation: possible risk indicator in normal tension glaucoma?

PURPOSE: Recently, the absence of spontaneous venous pulsation (SVP) has been suggested as a vascular risk factor for primary open-angle glaucoma (POAG). As the mechanism behind this phenomenon is still unknown, the authors have studied this vascular component using colour Doppler imaging (CDI). METHODS: A total of 236 patients were divided into three diagnostic groups: healthy controls (81), POAG (86) and normal tension glaucoma (NTG; 69). All subjects were submitted to CDI studies of the retrobulbar circulation, intraocular pressure measurements and assessment of SVP existence. Mann-Whitney, chi-square contingency tables and Spearman correlations were used to explore differences and correlations between variables in the diagnostic groups. RESULTS: Eighty-two percent of healthy controls had SVP (66/81), while a smaller numbers were registered in both glaucoma groups: POAG - 50% (43/86); NTG - 51% (35/69). In NTG patients, but not in POAG patients, the prevalence of the SVP phenomenon decreases with increased glaucoma damage (p = 0.04; p = 0.55, respectively). Overall glaucoma patients from both groups had lower central retinal vein (CRV) velocities than the healthy controls (p < 0.05). NTG patients with SVP had less severe visual field defects (mean defect -6.92 versus -11.1, p < 0.05), higher [correction added after online publication 21 September 2012; the word 'higher' has been inserted to replace the word 'lower'] peak systolic and mean flow velocities in the central retinal artery (p < 0.01; p < 0.05, respectively) as well as higher [correction added after online publication 21 September 2012; the word higher has been inserted to replace the word lower] maximal velocities and RI of the CRV (p < 0.02; p < 0.05, respectively). CONCLUSIONS: Glaucoma patients have a decrease in CRV velocities. SVP is less prevalent in glaucoma patients than in healthy individuals. This phenomenon apparently reflects different hemodynamic patterns in the central retinal vessels. This variable may be of particular importance in NTG patients, where it may be associated with more advanced functional damage.

Ophthalmic artery Doppler waveform changes associated with increased damage in glaucoma patients.

PURPOSE: To characterize Doppler waveform variables (early systolic acceleration [ESA] and systolic/diastolic mean velocity ratios [Sm/Dm]) of the Ophthalmic Artery (OA) by color Doppler imaging (CDI) in eyes with primary open-angle glaucoma (POAG). METHODS: Analysis of CDI examinations of the retrobulbar circulation of patients with POAG (n = 102), normal tension glaucoma (NTG, n = 89), and healthy controls (n = 59) by a condition-masked investigator. One-way ANOVA, chi-square, and Spearman's rank correlation tests were used to determine differences, establish comparisons, and to explore associations between variables, respectively. RESULTS: The overall Doppler waveform presented a shift to the right in the glaucoma groups, with significantly lower Sm/Dm ratios when compared to the control group (healthy: 2.94 ± 0.86, POAG: 2.60 ± 0.67, NTG: 2.63 ± 0.84; P = 0.01). ESA was significantly lower in the glaucoma groups (healthy: 688.8 ± 484 cm·s(-2), POAG: 548.1 ± 419 cm·s(-2), NTG: 548.5 ± 337 cm·s(-2); P = 0.03). No statistical differences were, however, detected in the OA velocities or resistance index (P ranged between 0.08 and 0.96). In the glaucoma groups, waveform parameters such as ESA, acceleration time, and systolic mean velocities correlated with systemic blood pressure variables (P < 0.05). In these groups, negative correlations were detected between Sm/Dm ratios and the degree of visual field defects (POAG: P = 0.01; r = -0.25) and retinal nerve fiber layer thickness (NTG: P = 0.02; r = -0.25). CONCLUSIONS: The pattern of blood flow velocities in the OA throughout the cardiac cycle seems to be altered in glaucoma patients. Further studies on how systemic blood pressure affects waveform variables in glaucoma patients may provide a better understanding of an underlying vascular dysfunction.

Success rate of miniplate anchorage for bone anchored maxillary protraction.

OBJECTIVE: To evaluate the success rate of Bollard miniplate anchorage for bone anchored maxillary protraction (BAMP). MATERIALS AND METHODS: Twenty-five consecutive patients (mean age, 12.0 ± 1.2 years; range, 8.7-14.8 years) with maxillary hypoplasia without congenital or acquired deformation were included in this study. A total of 100 Bollard modified miniplates were placed by the same surgeon. Ninety-nine miniplates were inserted under general anesthesia, and one was placed under local anesthesia because of initially soft bone conditions. Loading of the miniplates with 150 g elastics was initiated at 17.5 ± 6.9 days (range, 11-38 days) after surgery. Mean follow-up was provided at 20.8 ± 11.1 months (range, 6.5-46.2 months). RESULTS: The overall success rate of miniplate anchorage in terms of stability was 97%. During orthodontic loading, five miniplates showed signs of mobility. After interruption of loading over 2 months, two miniplates became stable again. However, a total of three miniplates needed to be removed and were successfully replaced under local anesthesia after a mean healing period of 3 months. CONCLUSION: Skeletal anchorage by means of Bollard modified miniplates is effective for BAMP. Success depends on proper presurgical patient counseling, minimal invasive surgery, good postsurgical instructions, and orthodontic follow-up.