Serum autoantibodies against hexokinase 1 manifest secondary to diabetic macular edema onset.

AIMS: Autoantibodies against hexokinase 1 (HK1) were recently proposed to be associated with diabetic macular edema (DME). We hypothesized that anti-HK1 autoantibodies can be used as DME markers and to predict DME onset. MATERIALS AND METHODS: Serum from patients with 1) DME, 2) diabetes mellitus (DM), 3) allergies or autoimmunities, and 4) control subjects was tested for anti-HK1 and anti-hexokinase 2 (HK2) autoantibodies by immunoblotting. Patients with DM were prospectively followed for up to nine years, and the association of anti-HK1 antibodies with new-onset DME was evaluated. The vitreous humor was also tested for autoantibodies. RESULTS: Among patients with DME, 32 % were positive for anti-HK1 autoantibodies (42 % of those with underlying type 1 DM and 31 % of those with underlying type 2 DM), and 12 % were positive for anti-HK2 autoantibodies, with only partial overlap of these two groups of patients. Anti-HK1 positive were also 7 % of patients with DM, 6 % of patients with allergies and autoimmunities, and 3 % of control subjects. The latter three groups were anti-HK2 negative. Only one of seven patients with DM who were initially anti-HK1 positive developed DME. CONCLUSIONS: Anti-HK1 autoantibodies can be used as DME markers but fail to predict DME onset.

Pars Plana Vitrectomy in the Treatment of Rhegmatogenous Retinal Detachment.

AIM: The aim of the study is to retrospectively evaluate the anatomical success rate and functional results of 25G+ PPV in the treatment of newly diagnosed rhegmatogenous retinal detachment (RRD). MATERIAL AND METHODS: The set consists of 152 eyes of 152 patients, of which 71 (47%) were men, average age 54 years, operated on by one surgeon for RRD at the Eye Clinic of the University Hospital and Medical Faculty of Masaryk University Brno from 1.7.2019 to 4.5.2021 using the 25G+ PPV technique. 25G+ PPV with pre-equatorial cerclage was performed on 7 patients. The patients' anamnesis included blunt ocular trauma and uncomplicated cataract surgery with implantation of a posterior chamber intraocular lens. The cause of RRD was retinal tear/s, regardless of their number and location. The transparency of the anterior segment of the eye enabled reliable visualization of the posterior segment. Preoperative proliferative vitreoretinopathy (PVR) grade A-D2 was admissible. Patients with a history of penetrating ocular trauma were excluded. The postoperative findings and functional outcomes of the patients were evaluated 1-3 months after PPV. The operation was anatomically successful if the retina was fully attached. Final visual acuity (VA) was evaluated for each patient. The final visual acuity examination was carried out typically on a Snellen optotype, either without correction, with the patient's own spectacle correction or with correction according to the current values on the autorefractometer. The arithmetic average was used for the numerical expression of the attained results, and the numerical values were also expressed in percentages. Since the different groups were not compared with each other, no statistical test was necessary to analyze the results. RESULTS: In 150 (98.7%) of the 152 patients in the group, we achieved complete retinal reattachment, in 2 (1.3%) patients the retina remained detached, and we recorded anatomical failure of the treatment. Fifty (33%) patients achieved VA ≥ 4/8. CONCLUSION: In 133 (87.5%) patients, we are able to state anatomical success even without the presence of intraocular tamponade in the operated eye. These patients can be considered completely cured. 25G+ PPV has demonstrated its contribution to resolving RRD.

Correlation Between Vitreous Level of Angiogenic Growth Factors and Oxygen Saturation in Retinal Vessels in Diabetic Retinopathy.

Purpose: The aim of this study was to investigate whether there is any association between the levels of the angiogenic growth factors and the vascular oxygen saturation in eyes with diabetic retinopathy. Methods: The study was designed as a prospective trial. The cohort consisted of 29 diabetic patients with scheduled vitreous procedures (intravitreal injection or pars plana vitrectomy). The control group included 30 patients scheduled for macular surgery (macular hole or epiretinal membrane). Nine patients (four from the diabetic maculopathy [DM] group and five from the control group) were excluded from the study because of unsuccessful vitreous samples. Retinal oximetry was performed several hours before the vitreous procedure was performed, and vitreous samples were obtained during the procedure. The concentrations of VEGF, Serpin F1/pigment epithelium-derived factor (PEDF), and placental growth factor (PlGF) were measured by ELISA. Results: A negative correlation between level of VEGF and arteriovenous (AV) saturation difference was determined in the DM group (Pearson correlation coefficient r = -0.607; two-tailed test, P = 0.002). Also a negative correlation between level of PlGF and AV saturation difference was determined in the DM group (Pearson correlation coefficient r = -0.521; two-tailed test, P = 0.011) A positive correlation between PlGF level and the vein saturation was not statistically significant (Pearson correlation coefficient r = 0.325; two-tailed test, P = 0.130). We did not find any correlation between vitreous level of PEDF and vascular saturation within the DM group. Conclusions: Our findings in diabetic patients suggests a correlation between the intravitreal level of proangiogenic factors and the AV difference measured by retinal oximetry.

Changes in oxygen saturation and the retinal nerve fibre layer in patients with optic neuritis - a pilot study.

PURPOSE: Assessment of retinal oxygen saturation, thickness of a retinal nerve fibre layer (RNFL) and functional changes in the optic nerve during optic neuritis (ON) in patients with multiple sclerosis (MS). METHODS: Thirty-two patients with ON due to MS within 3 months of onset of symptoms were enrolled [22 females, 10 males, age 34 ± 9 years, median 32.5 years, 22 patients with the clinically isolated syndrome (CIS), 10 patients with relapsing-remitting from of MS (RRMS)]. All patients were examined using optical coherence tomography (OCT model 4000, Carl Zeiss Meditec, Dublin, CA, USA), automatic optical oximetry (Oxymap ehf, Reykjavik, Iceland) and using visual evoked potentials (VEP) (Metronic Keypoint® , Minneapolis, MN, USA). RESULTS: Arterio-venous difference (AVD) was increased in patients ON affected eye compared to patients' unaffected eye (PUE) [34.2 ± 4.7 versus 31.3 ± 4.6, p = 0.044 (mean ± standard deviation)]. No statistically significant difference was found in vessel oxygen saturation as well as in RNFL thickness in ON affected eyes when compared to unaffected MS eyes and healthy individuals. Significantly lower optic nerve conduction velocity was found in the affected eye when compared to unaffected MS eye and healthy (p < 0.0001 for both comparisons). No correlation between oxygen saturation values and VEP was observed in patients with MS. CONCLUSION: The AVD in oxygen saturation is altered in patients with acute ON. In the early stage of ON, AVD could reflect inflammatory and metabolic changes in the affected eye. Therefore, oximetry could be used as another diagnostic method in MS patients in suspicion of ON. This result would be promising for future investigation in this field.

The effect of pars plana vitrectomy and nuclear cataract on oxygen saturation in retinal vessels, diabetic and non-diabetic patients compared.

PURPOSE: To determine the effect of pars plana vitrectomy (PPV) on oxygen saturation in retinal vessels in patients with diabetes and non-diabetes after a 1-year follow-up. METHODS: This was a prospective consecutive interventional case series in 82 eyes in 82 patients. The sample consisted of 25 patients with non-proliferative diabetic retinopathy with macular oedema based on vitreoretinal traction or epiretinal membrane (ERM) and 57 non-diabetic patients with macular hole and ERM. Automatic retinal oximetry (Oxymap Inc.) was used on all patients 24 hr prior to PPV, and it was also used 7 and 52 weeks after PPV (classic 20G or sutureless 23G). We analysed the data according to subgroup diagnosis and lens status. RESULTS: Arterial saturation increased significantly from 96.4 ± 2.9% at baseline to 96.6 ± 3.4% at week 7 and 97.3 ± 3.4% at week 52 (p < 0.0001; Friedman test). Vein saturation also increased significantly from 63.5 ± 7.9% at baseline to 66.1 ± 7.7% and 67.0 ± 7.2% at weeks 7 and 52 (p < 0.0001; Friedman test). The value of the arteriovenous (A-V) difference decreased significantly after vitrectomy from 32.8 ± 7.5% at baseline to 30.5 ± 7.5% and 30.3 ± 7.0% at weeks 7 and 52 (p < 0.0001; Friedman test). The subgroup analysis revealed that in patients with diabetes, there were no statistically significant changes in oxygen saturation in blood vessels or in the A-V difference after PPV. After vitrectomy, retinal vessel diameter reduced by about 3.5% in both groups of patients. Further, the analysis revealed that opacification of the lens leads to a decrease in oxygen saturation in contrast to a clear lens and pseudophakic IOLs. CONCLUSION: Oxygen saturation is higher in the retinal veins and arteries after PPV in patients with non-diabetes, and this lasts for at least 52 weeks. In contrast, in patients with diabetes, there is no increase in oxygen saturation in the retinal vessels after vitrectomy. After vitrectomy, retinal vessel diameter reduced in both groups of patients. Further, the nuclear cataract progression has substantial effect on oximetry results. Patients with nuclear cataract exhibited an increase in saturation in both arteries and veins, but the A-V difference remained the same.

Correlation of Vitreous Vascular Endothelial Growth Factor and Uric Acid Concentration Using Optical Coherence Tomography in Diabetic Macular Edema.

Purpose. We investigated two factors linked to diabetic macular edema (DME), vitreous and serum levels of vascular endothelial growth factor (VEGF) and uric acid (UA) in patients with DME, and compared the results with changes in optical coherence tomography (OCT) and visual acuity (VA). Methods. A prospective study of 29 eyes, 16 cystoid DME and nonproliferative diabetic retinopathy (DR) and 13 nondiabetic controls. Biochemical analysis of vitreous and serum samples was performed and OCT scans were graded according to central retinal thickness (CRT), cube volume (CV), cube average thickness (CAT), and serous retinal detachment (SRD). Results. In DME group, intravitreal concentrations of VEGF (p < 0.001), UA (p = 0.038), and total protein (p < 0.001) were significantly higher than in control group. In DME subjects, intravitreal UA correlated significantly with intravitreal VEGF (ƍ = 0.559, p = 0.03) but not with total vitreous protein and serum UA. Increased intravitreal VEGF in DME group correlated with increase in CV (ƍ = 0.515/p = 0.041). None of the OCT parameters correlated with the VA. Conclusions. The results suggest that the CV might be assessor of anti-VEGF therapy efficacy. Second, apart from VEGF, the role of UA in the pathogenesis and progression of DR should be considered.

The efficacy of ranibizumab treatment in clinical practice in patients with the wet form of age-related macular degeneration. The results of the Czech National Registry.

AIMS: The aim of this communication was to evaluate ranibizumab in the treatment of wet age-related macular degeneration. METHODS: Anonymised data on treatment efficacy and safety were consecutively entered into the Czech national database. From 01/09/2008 to 25/10/2011, 671 patients/685 eyes treated with ranibizumab monotherapy were entered in the registry. 454 ranibizumab treated eyes and 444 patients were monitored for 12-months. The dependent variable used to monitor disease progression and treatment results was change in visual acuity in the ETDRS (Early Treatment Diabetic Retinopathy Study) chart over time. RESULTS: After 12 months of treatment, a loss of < 15 letters in the ETDRS chart was found in 81.5% of eyes treated with ranibizumab. A gain of ≥ 15 letters was found in 9.7% of eyes on ranibizumab. The results for our patients treated in clinical practice with ranibizumab were poorer than those in the SUSTAIN (Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration) study. A rationale for this was sought in a sub-analysis. CONCLUSIONS: Sub-analysis demonstrated that treatment naive CNV (choroidal neovascularization), occult CNV and lower height of the macular oedema at the outset of the disease may be positive prognostic factors for final visual acuity in anti-VEGF (vascular endothelial growth factor) treated patients.

Prognostic factors of early morphological response to treatment with ranibizumab in patients with wet age-related macular degeneration.

Aim. To assess the significance of age, gender, baseline best corrected visual acuity, baseline macula thickness, and type and size of choroidal neovascularization in early morphological therapeutic response to ranibizumab treatment in patients with the wet form of age-related macular degeneration. Methods. From 09/2008 to 06/2013 we evaluated 1153 newly diagnosed, treatment-naïve patients treated with ranibizumab. Based on the morphological findings in the macula following the initial 3 injections of ranibizumab, the patients were divided into two groups based on active and inactive choroidal neovascularization. Results. After the initial 3 injections of ranibizumab, we examined the sample of 841 eyes with active CNV and 312 eyes with inactive CNV. In the inactive group, we found a statistically higher proportion of occult CNV (P < 0.001) and lower incidence of CNV greater than 5DA (P < 0.001) compared with the active group. We found no statistically significant difference in age, gender, baseline best corrected visual acuity, or baseline macula thickness between the inactive and active groups. Conclusion. Occult CNV and CNV smaller than 5DA are optimistic factors for a better morphological therapeutic response at the beginning of ranibizumab treatment.

Treatment of central serous chorioretinopathy with beta-blocker metipranolol.

AIM: The purpose of this study was to evaluate the effect of the systemically administered betablocker metipranolol on the course of central serous chorioretinopathy (CSC). METHODS: A prospective double-blind study involving 48 patients with a first attack of CSC not exceeding two weeks and who agreed to the follow-up ophthalmology examinations every week. The group was divided into a metipranolol group (n=23), receiving 10 mg of drug twice per day and a placebo group (n=25). The outcome measure was time in weeks from drug intervention (metipranolol vs. placebo) to reattachment of macula neuroepithelium. RESULTS: There was no statistically significant difference in duration of CSC in patients who used metipranolol and those who used placebo (P=0.341). CONCLUSIONS: In a prospective double-blind study, we found no effect of the betablocker metipranolol on the duration of central serous chorioretinopathy.

Progression of macular atrophy after PDT combined with the COX-2 inhibitor Nabumetone in the treatment of neovascular ARMD.

AIM: To evaluate photodynamic therapy (PDT) combined with the preferential the cyclooxygenase-2 (COX-2) inhibitor, nabumetone in the treatment of the neovascular age-related macular degeneration (ARMD). METHODS: A prospective, double-blind, randomized study on 60 patients with subfoveal CNV secondary to ARMD without any previous treatment. Patients were divided into a nabumetone or placebo group. The main endpoints were the change of best-corrected visual acuity (BCVA), central macular thickness (CRT) and number of required PDT treatments. RESULTS: In the nabumetone group, 27 patients (90%) and 28 (93%) in the placebo group completed the follow-up of 12 months. In the nabumetone group, the mean CRT decreased from 332 µm (SD 68 µm) to 220 µm (SD 46 µm). In the placebo group, CRT decreased from 331 µm (SD 72 µm) to 254 µm (SD 61 µm). The mean BCVA was 0.68 log MAR (SD 0.22 log MAR) in the nabumetone group and 0.62 log MAR (SD 0.23 log MAR) in the placebo group at baseline. This stabilised in the placebo group to 0.66 log MAR (SD 0.33) but deteriorated in the nabumetone group to 0.86 log MAR (SD 0.41 log MAR). There was a significant reduction in the number of required PDTs in the nabumetone group, but significant progression of the RPE atrophy area. CONCLUSION: Combined PDT with oral intake of the COX-2 inhibitor, nabumetone reduced the number of required PDT retreatments, but worsening BCVA caused by macular atrophy progression. Therefore the combination of the PDT with the nabumetone is not recommended.

The effect of pars plan vitrectomy on oxygen saturation in retinal vessels--a pilot study.

PURPOSE: To determine the effect of pars plana vitrectomy (PPV) on oxygen saturation in retinal vessels. METHODS: We performed a prospective consecutive interventional case series of 20 eyes of 20 patients with macular hole or epiretinal membrane. We performed automatic retinal oximetry (Oxymap Inc., Reykjavik, Iceland) in each patient 24 hr prior to and 45 days (range 42-49) after PPV (classic 20G or sutureless 23G). We analysed oxygen saturations in retinal arteries and veins. Vessel segments of first or second degree were selected. The same segment was analysed before and after PPV. Oximetry data were compared by paired two-tailed t-test. RESULTS: Pars plana vitrectomy did not alter arterial haemoglobin saturation with oxygen (98±2% prior to the surgery and 98±3% after the procedure, p=0.549). The mean venous haemoglobin saturation with oxygen increased after vitrectomy from 63±10% to 66±8% (p=0.012). CONCLUSIONS: Oxygen saturation is higher in retinal veins after pars plana vitrectomy. Further studies are needed to unveil the mechanism of how vitrectomy affects oxygen metabolism in the retina.

Cost and effectiveness of therapy for wet age-related macular degeneration in routine clinical practice.

PURPOSE: Evaluation of the cost and effectiveness of therapy for patients with the wet form of age-related macular degeneration (AMD) in routine clinical practice. METHODS: A retrospective multicentre evaluation of changes in the best-corrected visual acuity in applied kinds of therapy and a comparison with the cost of individual therapeutic procedures. RESULTS: An overall total of 788 eyes of 763 patients with an average age of 73.2 ± 8.6 years was evaluated for a 1-year minimum period. In the ranibizumab and pegaptanib therapy groups, a reduction of 1.3 letters (p = 0.303) and 1.4 letters (p = 0.197) was found, respectively. In the group of photodynamic therapy (PDT) with verteporfin, a reduction of 5.2 letters was achieved (p < 0.001). Under the conditions of routine practice in the Czech Republic, the annual cost is highest (EUR 5,467.63/patient) in patients with pegaptanib therapy. The annual cost in patients with ranibizumab therapy is lower by EUR 1,220.16. The cost is nearly half (EUR 2,783.65) in the group treated with PDT with verteporfin. CONCLUSION: An initiation of AMD therapy by ranibizumab is cost-effective as compared to pegaptanib. Both ranibizumab and pegaptanib are significantly more efficient as compared to PDT with verteporfin. Therapy with ranibizumab and pegaptanib, as compared to PDT with verteporfin, prevents the loss of 1 line of vision on the ETDRS chart for EUR 1,225.98 and 2,286.18, respectively.

Effects of treatment change in patients with neovascular age-related macular degeneration; results from the Czech National Registry.

AIMS: To determine the effectiveness of second line treatments in patients with neovascular AMD who did not respond adequately to primary treatment. METHODS: Retrospective, multicentre assessment. The frequency of primary treatment failure and outcomes of subsequent secondary treatment were assessed according to the type of primary treatment, type of CNV and change in BCVA over a 12 month period. RESULTS: At the time of assessment 750 entries (750 treated eyes, 725 treated patients) had follow-up longer than 12 months. A treatment change required 7.7% subjects treated with ranibizumab, 20.5% with pegaptanib and 22% with PDT and verteporfin. Average BCVA of all patients at the beginning of primary treatment was 50.7 ± 3 letters and 43 ± 3.5 letters in 12(th) month (P<0.001). The mean decrease in BCVA was 7.7 ± 0.6 letters during the first 6 months of observation. During the next 6 months, no significant change occurred. The change of primary therapy was required on average after 6.5 ± 2.1 months. CONCLUSION: BCVA loss was the most significantly decelerated in patients who received ranibizumab as a secondary therapy following unsuccessful treatment with pegaptanib sodium.

The in vitro antimicrobial activity of silicone oils used in ophthalmic surgery.

BACKGROUND: The aim of the study was in vitro assessment and comparison of the antimicrobial activity of three types of silicone oils used in ophthalmic surgery. METHODS: The silicone oils (Arciolane 1300 centistokes, Arciolane 5500 centistokes and Oxane Hd, heavy silicone oil) were inoculated with microbes common in endophthalmitis and their growth was observed continuously. Control tests of microbial growth were performed on silicone oil-free media, i.e. saline and standard enrichment media. In both tested oils and control media, the microbes were cultured aerobically for 21 days, bacteria at 37 °C and yeasts and fungi at 30 °C. Prior to and during incubation at given intervals (days 0, 2, 4, 7, 9, 11, 14, 16, 18 and 21), 10 µl samples were taken from all test tubes. These were diluted in saline in a series of test tubes, with the minimum concentration reaching 10(-8). From each dilution, 25 µl were inoculated onto agar media. After 24 h of aerobic incubation at 37 °C (bacteria) and 48 h at 30 °C (yeasts and fungi), the grown colonies were counted and the numbers of colony-forming units in 1 ml (CFU/ml) were determined. RESULTS: In vitro, the highest antimicrobial effect was observed for the Oxane Hd silicone oil. CONCLUSIONS: If endophthalmitis is treated by pars plana vitrectomy, the application of Oxane Hd silicone oil into the vitreous cavity at the end of surgery may contribute to the elimination of microorganisms from the intraocular space but clinical trials are needed to assess its safety.

Initial visual acuity is an important prognostic factor in patients with branch retinal vein occlusion.

PURPOSE: To evaluate the role of initial visual acuity (VA) as a potential prognostic factor for final VA in patients with branch retinal vein occlusion (BRVO). METHODS: A retrospective data analysis involving 163 patients with macular edema secondary to BRVO treated according to the recommendations of the Branch Vein Occlusion Study Group was performed using univariate and multivariate logistic regression models, and receiver-operating characteristics analysis. The analyses take factors into account that can potentially influence final visual result: sex, age, type of occlusion (major temporal or macular), grid photocoagulation and ischemia. RESULTS: The final VA ≤ 0.1 was statistically significantly related to initial VA ≤ 0.16 and age > 70 years. Sex, type of occlusion, grid photocoagulation and ischemia did not significantly influence the prediction of final VA based on age and initial VA. CONCLUSIONS: The analysis shows that initial VA and age > 70 years significantly influence the prognosis for final visual results in patients with BRVO.