Pneumatic displacement with intravitreal tPA injection versus vitrectomy with sub retinal tPA injection in small and medium sub macular hemorrhages- a multicenter comparative study.

PURPOSE: Comparing between the visual outcomes and post operative complications of two surgical treatments for sub macular hemorrhage, pars plana vitrectomy with tissue plasminogen activator (tPA) injection procedure, and pneumatic displacement of submacular hemorrhage with intravitreal tPA injection. METHODS: A retrospective chart review of patients with sub macular hemorrhage (SMH) was performed. Data was collected from 150 patients with sub macular hemorrhage. Patients were followed up from the day of admission and up to a year post surgery. Evaluation included visual acuity, optical coherence tomography (OCT), fundus examination and rates of complications. RESULTS: Pars plana vitrectomy procedure has showed a better visual outcome in small SMH. Comparing complications between the two treatment modalities, no significant difference has been found in the study. CONCLUSIONS: Pars plana vitrectomy and tPA showed a clear advantage with a trend of better visual acuity as well as a significant predictor to better visual acuity for small and medium sub macular hemorrhage.

Early versus delayed photodynamic therapy for chronic central serous chorioretinopathy.

PURPOSE: Central serous chorioretinopathy (CSCR) patients are sometimes referred to Photodynamic Therapy (PDT) with very long-term disease. The purpose of this study was to analyze the results of PDT in CSCR eyes with long-standing disease. METHODS: The medical records of the patients that underwent PDT for CSCR between 2009 and 2019 were reviewed. Cases were divided into two groups based on the duration of disease before PDT treatment: early treatment (3 to 6 months) and delayed treatment (longer than 6 months). The treatment was defined as successful when the subfoveal fluid was absorbed during follow-up. RESULTS: The PDT treatment was successful in 76% and 77% of eyes in the early and delayed treatment groups, respectively. Both groups showed significant improvement in central retina measurements at the 3-months follow-up which persisted to the last follow-up visit. The visual acuity (VA) at baseline was significantly worse in the delayed treatment group (0.5 ± 0.26 vs. 0.3 ± 0.24, P = 0.042) and improved in both groups but remained low in the delayed treatment group during the study. CONCLUSION: We suggest that if CSCR is not spontaneously improving over 3 months the patient should be offered PDT, to prevent VA loss from the long-term presence of subretinal fluid in the macula. PDT is not associated with loss of vision in eyes with chronic CSCR, and can be safely used in eyes with relatively good VA.

The Effect of Syringe-Filling Technique on the Risk for Endophthalmitis after Intravitreal Injection of Anti-VEGF Agents.

PURPOSE: This study aimed to compare the risk for post-injection endophthalmitis between different anti-vascular endothelial growth factor (VEGF) agents and syringe preparation techniques. METHODS: A retrospective study of anti-VEGF injections performed in 3 large ophthalmology departments between 2013 and 2019 was conducted. Injections were categorized according to the drug and the syringe-filling technique - prefilling by a hospital pharmacy, prefilling by a good manufacturing practice (GMP) pharmacy, self-drawing from the vial by the injecting physician, and use of a prefilled syringe. Cases of endophthalmitis were identified, and their rates were analyzed. RESULTS: A total of 197,402 injections were included, and 53 cases of endophthalmitis were identified (0.027% risk). The risk of endophthalmitis following injections with syringes that were prefilled by GMP pharmacies or the manufacturers was significantly lower than that following injections which were self-drawn by the physician (0.019% vs. 0.055%, p < 0.0001). For ranibizumab, risk of endophthalmitis decreased since it became available in a prefilled syringe (0.054% vs. 0.014%, p = 0.066), bordering on statistical significance. CONCLUSIONS: The syringe-filling technique is an important factor determining risk of post-injection endophthalmitis. Use of GMP-grade prefilling by professional pharmacies or the manufacturers significantly reduces this risk and should be the technique of choice for all drugs administered by intravitreal injection.

Detecting intrinsic global geometry of an obstacle via layered scattering.

Given a closed k-dimensional submanifold K, encapsulated in a compact domain M ⊂ E, k ≤ n - 2, we consider the problem of determining the intrinsic geometry of the obstacle K (such as volume, integral curvature) from the scattering data, produced by the reflections of geodesic trajectories from the boundary of a tubular ϵ-neighborhood T ( K , ϵ ) of K in M. The geodesics that participate in this scattering emanate from the boundary ∂ M and terminate there after a few reflections from the boundary ∂ T ( K , ϵ ). However, the major problem in this setting is that a ray (a billiard trajectory) may get stuck in the vicinity of K by entering some trap there so that this ray will have infinitely many reflections from ∂ T ( K , ϵ ). To rule out such a possibility, we modify the geometry of a tube T ( K , ϵ ) by building it from spherical bubbles. We need to use ⌈ dim ⁡ ( K ) / 2 ⌉ many bubbling tubes { T ( K , ϵ ) } for detecting certain global invariants of K, invariants that reflect its intrinsic geometry. Thus, the words "layered scattering" are in the title. These invariants were studied by Hermann Weyl in his classical theory of tubes T ( K , ϵ ) and their volumes.

Varieties of political support in emerging democracies: A cross-national analysis.

Political support is a multidimensional construct encompassing evaluations of political leaders and institutions (specific support) as well as adherence to basic regime principles (diffuse support). Scholars have traditionally assumed that diffuse and specific support are driven by different forces and evolve largely independently. Prior empirical work, however, has struggled to untangle the two support dimensions and focused predominantly on cross-national differences, ignoring their dynamics. This paper develops an analytical and empirical approach to examine the levels and dynamic interplay of both support dimensions and estimate their determinants, applying it to South American democracies between 1996 and 2015. Contrary to received wisdom, we show that both dimensions are quite volatile and closely linked in this region. In particular, negative economic shocks not only undermine support for government actors, but also fuel democratic disenchantment. Nonetheless, while regime support is rather fickle in South America, it can be ultimately resistant to performance fluctuations.

Age differences in clinical manifestation and prognosis of thyroid eye disease.

PURPOSE: To examine the clinical differences in manifestation, course, treatment, and prognosis of thyroid eye disease (TED) in patients younger than 40 years of age at diagnosis compared to older patients. METHODS: Medical record review of 131 TED patients was performed. The patients were divided into two age groups, Group 1 ≤ 40 years (23 patients) and Group 2 > 40 years (108 patients). RESULTS: Younger patients had more eyelid retraction and proptosis at initial presentation, whereas older patients were more likely to have diplopia (P = 0.001). Acute inflammatory signs were more common in the Group 2 patients (P = 0.04). Corrected visual acuity was 20/20 and 20/25 in both groups. Optic neuropathy was diagnosed only in Group 2 patients (n = 12; 11 %), and it resolved after steroids or orbital decompression surgery in all cases. The mean follow-up time was 36 months (36 ± 7.7; 59.3 ± 5.8). Systemic steroid use, orbital surgery, and strabismus surgery were more common in Group 2 (P < 0.0001, P < 0.05 respectively). CONCLUSIONS: TED under the age of 40 years has different clinical features. In our group of younger patients, the clinical presentation was milder than in the older group with a higher rate of lid retraction and proptosis and lower rate of restrictive myopathy and optic neuropathy. Their disease course was less severe and required less aggressive medical treatment and less surgical procedures.

Intracameral cefuroxime and the incidence of post-cataract endophthalmitis: an Israeli experience.

PURPOSE: The European Society of Cataract & Refractive Surgeons (ESCRS) study reported a decrease in endophthalmitis rates from 0.34 % to 0.08 % with the use of intracameral cefuroxime. The purpose of this study was to compare the endophthalmitis rates before and after the introduction of intracameral cefuroxime (ICC) routinely at the end of cataract surgery. METHODS: A retrospective consecutive cohort study. We compared the rates of endophthalmitis between the years 2000-2006, and the years 2007-2014, after the pivotal publication of the ESCRS. Data collected included age, gender, culture results, initial and final visual acuity, and complications. Only patients that presented with endophthalmitis following cataract surgery performed at the two centers were included. RESULTS: Twenty-two cases of endophthalmitis occurred between the years 2000 and 2006, out of 26,663 cataract operations performed at the two centers, a rate of 0.083 %. Ten cases occurred between the years 2007 and 2014 out of 29,431 cataract operations, a rate of 0.034 %. The difference was statistically significant (p = 0.03) CONCLUSIONS: The introduction of prophylactic use of intracameral cefuroxime was associated with a significant reduction in post-operative endophthalmitis rates in our centers. We strongly recommend adoption of this routine by for all cataract operations except when contraindicated.

SWITCHING TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FROM BEVACIZUMAB TO RANIBIZUMAB: Who is Likely to Benefit From the Switch?

PURPOSE: To evaluate the safety and efficacy of switching from bevacizumab to ranibizumab in patients with neovascular age-related macular degeneration. METHODS: Retrospective study of patients with neovascular age-related macular degeneration initially treated with bevacizumab and switched to ranibizumab. Visual acuity and central retinal thickness (CRT) were retrieved at four time points: before the last three bevacizumab injections, at the switch, after the first three ranibizumab injections, and at the end of follow-up. RESULTS: One hundred and fourteen eyes of 110 patients were included. Switching from bevacizumab to ranibizumab did not achieve a significant change in visual acuity, and a significant reduction in CRT was achieved after the first three injections but was not maintained by the end of follow-up. Eyes that lost ≥0.1 logMAR before the switch were more likely to improve in visual acuity (P = 0.013), and eyes with ≥10% increase in CRT before the switch were more likely to improve anatomically (P = 0.0003). In 47.3% of the eyes, the CRT was reduced by ≥10% after the first 3 ranibizumab injections, and the reduction was maintained with additional injections. CONCLUSION: Switching to ranibizumab should be considered in patients with visual acuity decrease or CRT increase, despite monthly bevacizumab injections. The response should be evaluated after the first three injections to guide future treatment.

[The revolution in the treatment of retinal diseases: anti-VEGF treatment at the Assuta Eye Institute].

The VEGF protein (Vascular Endothelial Growth Factor) was identified in the '80s as a factor which induces proliferation of blood vessels in the body in general and in the retina in particular. Proliferative processes in retinal blood vessels, vascular permeability and induced edema which follows, frequently cause blindness in the diseases of the macula: AMD (Age-related Macular Degeneration) diabetes and retinal vascular occlusions. Since 2006, through treatment using anti-VEGF drugs--Avastin (Bevacizumab) and Lucentis (Ranibizumab) and Eylea (Aflibercept)--blindness in many patients in Israel and elsewhere was prevented. This paper reviews the treatment with anti-VEGF intraocular injections in the above mentioned diseases with reference to the growing activity at the Assuta Eye Institute.

Aflibercept monotherapy or bevacizumab first for diabetic macular edema.

PURPOSE: Clinical outcome and switch patterns with bevacizumab first treatment strategy for patients with newly diagnosed neovascular age-related macular degeneration (nAMD). METHODS: Retrospective observational study of the number of intravitreal injections of bevacizumab and treatment switch in patients who started intravitreal bevacizumab injections between January 1, 2016 and December 30, 2018. RESULTS: From January 1 2016 to December 31 2018, 608 eyes of 565 patients started intravitreal injections of bevacizumab for a new diagnosis of nAMD. Average visual acuity (VA) at presentation was 0.60 logarithm of the minimum angle of resolution (logMAR), which improved to 0.47 after six injections (P < 0.001) and decreased to 0.63 at the last follow-up (P = 0.543). Switch of treatment was recommended for 190 eyes (31.3%), and of them, 91 patients (15%) were switched during the first 6 months and defined as primary failure of bevacizumab. The switch of treatment resulted in a statistically significant improvement in VA in the first 6 months after the switch. The gain in VA was not sustainable over time. CONCLUSION: Bevacizumab first treatment strategy produced results that were comparable to previous real-world outcomes publications of ranibizumab and aflibercept treatment with low rates of failure of bevacizumab treatment. Treatment switch to second-line treatment yielded a significant VA improvement, mainly in patients with primary bevacizumab failure.

Ocular Surface Temperature Profile of Eyes with Retinal Vein Occlusion.

Retinal vein occlusion (RVO) results in ischemia followed by an inflammatory response. Both processes affect tissue temperature in opposite directions. Here, we evaluate the effect of RVO on the ocular surface temperature (OST) profile. Subjects with RVO were prospectively recruited. Healthy subjects without any ocular disease served as controls. The OST was determined using the Therm-App thermal imaging camera, and image processing software was employed to compute the mean temperature values of the medial canthus, lateral canthus, and cornea. We obtained thermographic images from 30 RVO subjects (30 eyes) and 148 controls (148 eyes). A univariate analysis found that eyes with RVO had significantly elevated OSTs compared to the controls (mean difference of 0.6 ± 0.3 Celsius, p < 0.05). However, this distinction between the groups lost statistical significance upon adjusting for possible confounders, including patient and environmental factors. These findings were confirmed with a post hoc case-control matched comparison. In conclusion, RVO does not seem to affect the OST. This might be due to the balance between inflammatory thermogenesis and heat constriction from ischemia in RVO. It is also possible that, in our cohort, the RVO pathophysiological processes involved were localized and did not extend to the anterior segment. Patient and environmental factors must be considered when interpreting the OST.

Effectiveness at 1 year of monthly versus variable-dosing intravitreal ranibizumab in the treatment of choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To evaluate the visual acuity results of monthly ranibizumab injections compared with a variable-dosing schedule for the treatment of neovascular age-related macular degeneration. METHODS: A retrospective study that compared two cohorts of consecutive patients. All patients were treatment naive, with baseline visual acuity of 20/400 or better, and completed 12 months of therapy. In the first group all patients received monthly injections. In the other group, after 3 monthly loading doses, a variable-dosing schedule was used, based on a monthly clinical assessment and optical coherence tomography. RESULTS: Fifty-six consecutive patients (60 eyes) were included. At 12 months the median number of injections were 12 and 8, respectively, and the mean change in Snellen visual acuity was an improvement of 0.27 logarithm of the minimum angle of resolution in the monthly treated group versus 0.21 logarithm of the minimum angle of resolution improvement in the variable-dosing group (P = 0.53). In the monthly treated group 96.8% of eyes lost <0.3 logarithm of the minimum angle of resolution versus 96.6% of eyes in the variable-dosing group (P = 1.0). CONCLUSION: We were able to show that in our clinical setting patients achieved similar visual acuity results with either monthly injections or with a variable-dosing protocol. There was a trend toward better results with monthly treatment.

The Role of Anterior Chamber Depth on Post-operative Refractive Error After Phacovitrectomy.

PURPOSE: To investigate the effect of phacovitrectomy on the post-operative anterior chamber depth (ACD) and refractive outcomes, and to analyze the potential differences between vitreous filling with BSS, air and gas. METHODS: Patients who underwent phacovitrectomy were included in this study and invited for repeated post-operative examination including refraction and biometry at least 3 months after the surgery. Data retrieved included demographic information, indication for phacovitrectomy, surgical details, type of vitreous filling (BSS, air or gas), pre-operative and post-operative biometric data including K-readings, axial length (AL), and ACD, as well as spherical equivalent (SE) values of the target and final refraction. RESULTS: Forty-three eyes of 43 patients were included in this study, including 10 eyes filled with BSS, 18 with air and 15 with gas. The mean difference between the final measured spherical equivalent (SE) and the SE of the intended target refraction was 0.61±0.68 D (p = 0.019). Only 58.1% of eyes had a final SE within ±0.5D of the target refraction. Following surgery, AL remained unchanged, while mean pre-operative ACD increased significantly from 3.11±0.34 mm to 4.77±0.47 mm (p < 0.001). There was no difference in refractive error between the vitreous fillings and no correlation with AL or ACD. CONCLUSIONS: Phacovitrectomy is associated with lower accuracy of post-operative refraction compared to cataract surgery. This may be attributed to a significant change in ACD, influencing the effective lens position of the IOL, and may require adjustment of the pre-operative calculations.

Mesopic foveal contrast sensitivity is impaired in diabetic patients without retinopathy.

BACKGROUND: Contrast sensitivity (CS) has been studied extensively to determine its effectiveness as a test for diagnosing early and advanced diabetic retinopathy. Various techniques have been adopted to measure CS, and most of them reported a significant difference between diabetic and normal eyes. Our purpose is to demonstrate differences in foveal CS between diabetic patients without retinopathy and healthy subjects under mesopic and photopic conditions, using a simple, rapid computerized test. METHODS: Seventeen eyes of nine patients with type 2 diabetes without diabetic retinopathy were included. Fourteen eyes of seven non-diabetic patients served as controls. All the patients underwent a careful ophthalmologic examination, including ETDRS chart visual acuity, color photographs, and optical coherence tomography (OCT). Patients with any ocular disease were excluded. All eyes had a visual acuity of 20/25 or better, a normal eye examination and optical coherence tomography (OCT). Photopic and mesopic contrast sensitivity was tested using a computerized psychophysical static method involving four forced-choice procedures. The targets were Gabor patches with spatial frequencies of 3-12 cycles per degree (cpd). The mesopic testing was conducted in a completely darkened room; the monitor was covered with a neutral density filter, allowing luminance of only 0.9 cd/m(2). RESULTS: The average age was similar: 59.1 ± 5.3 years in the diabetic group vs 61.4 ± 3.2 years in the control group. The average duration of diabetes was 16 years (range 6-26). The average visual acuity was 0.04 ± 0.01 logMAR and 0.01 ± 0.01 logMAR in the diabetic and control groups respectively. Photopic foveal CS was similar in both groups. Significantly lower CS was found in diabetic patients under mesopic conditions at a spatial frequency of 3 (p < 0.008). At higher spatial frequencies, the mesopic contrast sensitivity was very low in both groups and without a significant difference. CONCLUSIONS: Mesopic foveal CS is impaired in diabetic patients despite good visual acuity, a normal fundus examination and normal OCT. Early central visual function impairment may occur in diabetic patients before the appearance of retinopathy.

Ranibizumab for persistent diabetic macular edema after bevacizumab treatment.

PURPOSE: To evaluate the efficacy of switching from bevacizumab to ranibizumab in patients with diabetic macular edema (DME). METHODS: This was a retrospective study of patients with DME initially treated with bevacizumab and switched to ranibizumab. Visual acuity (VA) and central retinal thickness (CRT) were retrieved at fixed timepoints prior to and after the switch. RESULTS: Forty eyes of 32 patients were included in the study. The difference in VA between any of these fixed timepoints was not statistically significant. A significant gain in VA was found in eyes that lost more than 0.1 logMAR during treatment with the last 3 bevacizumab injections. The mean CRT was significantly lower after the first 3 ranibizumab injections and at the final follow-up (p<0.001), a 67 ± 14 µm and 78 ± 18 µm reduction in thickness, respectively. CONCLUSIONS: Switching to ranibizumab resulted in a significant decrease in the CRT of eyes with DME, and should be considered when there is a lack of response or deterioration while on bevacizumab injections. A significant gain in VA was observed in a subgroup of eyes that lost more than one line while receiving the last 3 bevacizumab injections prior to the switch.

Endophthalmitis today: a multispecialty ophthalmology department perspective.

PURPOSE: To portray the current scene of endophthalmitis in a multispecialty ophthalmology department regarding etiologies and treatment guidelines. METHODS: Retrospective chart review of all patients diagnosed with endophthalmitis or suspected endophthalmitis from 2009 to 2012. RESULTS: A total of 24 eyes were diagnosed with endophthalmitis or suspected endophthalmitis during a 4-year period. The etiologies included endogenous endophthalmitis (6), blebitis (3), Ahmed valve implantation (3, 2 of them with late infection), postcataract surgery (3), intravitreal injections (4), penetrating injury (2), and other surgical procedures (3). Of the postcataract surgery cases, 1 was a congenital cataract surgery, and 2 were referrals. There were no endophthalmitis cases in 4603 adults undergoing cataract surgery in our department during this period. There were 14 positive cultures: 1 was candida and the rest bacteria. Ten of the bacteria cases were Gram-positive cocci (predominantly strep species), 3 were Gram-negative, and coagulase negative staphylococci were detected in 2 cases. CONCLUSIONS: Our study indicates a significant change in the case mix of endophthalmitis. The past leading cause, cataract surgery, was dramatically reduced, and intravitreal injections became a major cause. The change in etiologies, and possibly in the microbial flora, warrants reconsideration of the rules that guided the management of endophthalmitis since the Endophthalmitis Vitrectomy Study.

Effect of ocriplasmin on the management of macular holes: assessment of the clinical relevance of ocriplasmin.

IMPORTANCE: Assessing the effect of ocriplasmin availability on the management of full-thickness macular holes (MHs) is important for vitreoretinal surgeons and their patients. Such an assessment can indicate whether the use of ocriplasmin will bring a paradigm shift in treating MHs or will be just an additional option relevant to a small group of patients. OBJECTIVES: To classify the MHs evaluated in our institute by their stage and the presence of vitreomacular adhesion (VMA) and to identify eyes that were suitable candidates for ocriplasmin injection according to guidelines published by the Microplasmin for Intravitreous Injection-Traction Release Without Surgical Treatment (MIVI-TRUST) study group. DESIGN, SETTING, AND PARTICIPANTS: All optical coherence tomographic studies of eyes with MHs performed between 2009 and 2013 were retrospectively reviewed. The scans were interpreted by 2 individuals, and for each hole the stage, size, and vitreomacular relationship were defined according to the definitions used in the MIVI-TRUST studies. One hundred thirty-five patients with full-thickness MHs evaluated at a public hospital were included in the study series. There were 82 women and 53 men, and the mean (SD) age was 67.3 (12.8) years. MAIN OUTCOMES AND MEASURES: The stage, size, and presence or absence of VMA were documented for each MH. The suitability for ocriplasmin intravitreal injection was determined according to the criteria described in the MIVI-TRUST reports. RESULTS: Vitreomacular adhesion was present in 19 eyes with MH (14.1%). Of these, the hole size was 400 µm or less in only 9 eyes (6.7% of the series). Using the criteria of the MIVI-TRUST study exclusively, only these eyes were candidates for ocriplasmin injection. Assuming a closure success rate of 40%, as described in that study, only 2.7% of the patients in our series would have benefited from ocriplasmin injection. CONCLUSIONS AND RELEVANCE: Our findings indicate that ocriplasmin injection is an adequate choice for few patients with MHs. Pars plana vitrectomy will probably remain the treatment of choice for most eyes with MHs. This situation could change if MHs are detected earlier and treated while they are still small and have vitreomacular traction.

Postoperative treatment with topical diclofenac versus topical dexamethasone after combined phacotrabeculectomy with mitomycin C.

OBJECTIVE: The objective of the study was to compare the efficacy and safety of topical dexamethasone sodium phosphate 0.1% (Sterodex) to diclofenac sodium 0.1% (Voltaren Ophthalmic) after combined phacotrabeculectomy with mitomycin C. METHODS: This prospective, randomized, double-masked clinical trial includes 42 patients with glaucoma and cataract who underwent a combined phacotrabeculectomy. Patients were randomly assigned to postoperative treatment with topical diclofenac sodium 0.1% or topical dexamethasone phosphate 0.1%. Follow-up duration was 12 months and all examinations were masked. The main outcome measures were intraocular pressure (IOP), number of glaucoma medications, and bleb morphology. RESULTS: Baseline characteristics of the diclofenac (n=21) and dexamethasone (n=21) patients were similar. Phacotrabeculectomy with both postoperative treatments was effective in reducing IOP, lowering the number of glaucoma medications and improving visual acuity at all follow-up points. The average number of medications taken by the dexamethasone group was significantly greater than the diclofenac group at 8 months (1.2 ± 1.4 and 0.3 ± 0.6, respectively, P=0.03). The mean bleb height of the diclofenac group was significantly higher than the dexamethasone group at 3 weeks (P=0.05), and the mean bleb width was significantly wider at 8 months (P=0.04). No significant group differences in IOP were found at any of the follow-up visits, although there was a clinical trend toward lower IOP values in the diclofenac group. Sixteen patients (76%) in the diclofenac group and 17 patients in the dexamethasone group (81%) completed 1 year of follow-up. CONCLUSIONS: In this preliminary study, diclofenac sodium is at least as good as topical dexamethasone phosphate for glaucoma patients undergoing two-site combined phacotrabeculectomy with mitomycin C.