The effect of combination therapy with intravitreal bevacizumab and topical timolol-dorzolamide eye drops on diabetic macular edema: a double-blind randomized controlled trial.

BACKGROUND: The mainstay of treatment in diabetic macular edema (DME) is intravitreal administration of anti-vascular endothelial growth factors (anti-VEGFs). Aqueous depressants may enhance the effects of anti-VEGF agents by prolonging their clearance via aqueous outflow. PURPOSE: To compare the anatomical and functional outcomes of treatment with intravitreal bevacizumab (IVB) and topical timolol-dorzolamide versus IVB alone. METHOD: In this randomized placebo-controlled clinical trial, patients with center-involving DME (ci-DME) and best corrected visual acuity (BCVA) of 20/30 or less were enrolled and randomly allocated to two treatment arms. One group received three monthly IVB injections and timolol-dorzolamide eye drops twice a day (IVB + TD group); the other group received three monthly IVB injections and artificial tear drops as placebo (IVB group). Patients underwent ophthalmic evaluations and macular optical coherence tomography scans at baseline and 1 month after the third injection. RESULT: Forty-six eyes from 46 patients with ci-DME were recruited. There was no intergroup difference regarding age, gender distribution, diabetic retinopathy stage, glycemic indices, BCVA, central macular thickness (CMT), or intraocular pressure at baseline. BCVA was significantly improved in the IVB + TD group (0.46 ± 0.18 to 0.36 ± 0.18 logarithm of the minimum angle of resolution [logMAR], p = 0.002), in contrast to IVB group (0.40 ± 0.17 to 0.35 ± 0.22 logMAR, p = 0.113). Similarly, the IVB + TD group showed a significant reduction in CMT (p < 0.001), unlike the IVB group (p = 0.086); and the CMT change in the former was greater than in the latter (- 0.57 ± 57.67 vs. - 25.52 ± 68.02 µm, p = 0.033). CONCLUSION: Our findings support the short-term effectiveness of topical timolol-dorzolamide as adjunctive therapy to IVB injections in managing center-involving DME in terms of anatomical and visual outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT05083689 (October 19, 2021).

Corneal Epithelial Thickness Mapping: A Major Review.

The corneal epithelium (CE) is the outermost layer of the cornea with constant turnover, relative stability, remarkable plasticity, and compensatory properties to mask alterations in the underlying stroma. The advent of quantitative imaging modalities capable of producing epithelial thickness mapping (ETM) has made it possible to characterize better the different patterns of epithelial remodeling. In this comprehensive synthesis, we reviewed all available data on ETM with different methods, including very high-frequency ultrasound (VHF-US) and spectral-domain optical coherence tomography (SD-OCT) in normal individuals, corneal or systemic diseases, and corneal surgical scenarios. We excluded OCT studies that manually measured the corneal epithelial thickness (CET) (e.g., by digital calipers) or the CE (e.g., by confocal scanning or handheld pachymeters). A comparison of different CET measuring technologies and devices capable of producing thickness maps is provided. Normative data on CET and the possible effects of gender, aging, diurnal changes, refraction, and intraocular pressure are discussed. We also reviewed ETM data in several corneal disorders, including keratoconus, corneal dystrophies, recurrent epithelial erosion, herpes keratitis, keratoplasty, bullous keratopathy, carcinoma in situ, pterygium, and limbal stem cell deficiency. The available data on the potential role of ETM in indicating refractive surgeries, planning the procedure, and assessing postoperative changes are reviewed. Alterations in ETM in systemic and ocular conditions such as eyelid abnormalities and dry eye disease and the effects of contact lenses, topical medications, and cataract surgery on the ETM profile are discussed.

RONA Technique: A Novel ILM Peeling Method for Treatment of Large Full-Thickness Macular Holes.

PURPOSE: To present a new technique, RONA, for internal limiting membrane peeling and show its comparable success rate in closure of large full-thickness macular holes (FTMHs). METHODS: This prospective interventional case series was implemented from January 2018 to November 2019. Consecutive cases with large FTMH with an aperture size of more than 500 µ m were included. The RONA technique was used to make consecutive flaps; the central border of which remained adherent to the FTMH edge. The emphasis is that the central border of all flaps should remain adherent to the FTMH edge, letting the flaps remain there spontaneously. RESULTS: Seventeen eyes of 17 patients (4 males and 13 females; age 62.3 ± 7.8 years) were included. The mean size of opening and base of FTMH were 651.1 ± 141.1 µ m (range: 501-950) and 964.6 ± 383.8 µ m (range: 527-2098), respectively. One week after the surgery, complete closure of all FTMHs occurred with no hole reopening until the end of 12 months. The mean best-corrected visual acuity at baseline and 12 months after surgery were 1.57 ± 0.30 and 0.75 ± 0.028 logarithm of the minimum angle of resolution, respectively, with statistically significant improvement ( P < 0.001). CONCLUSION: The first advantage of this efficacious technique is that there is no need to manipulate FTMH edge or underneath tissues. Another and of course, the most important advantage is that there is no need to care about flap unfolding during the exchange stage.

Smoking and environmental tobacco smoke exposure: implications in ocular disorders.

PURPOSE: This article aims to gather and review the available knowledge on several implications of smoking and environmental tobacco smoke (ETS) exposure in ocular disorders and provides pathomechanistic insights where applicable. MATERIALS AND METHODS: PubMed and Scopus databases were searched for relevant studies on the association of smoking and ETS exposure with various ocular disorders. Studies with different evidence levels, e.g., in-vivo, case-control, cohort, and meta-analysis, were included. RESULTS: Smoking is an established, modifiable risk factor in several ocular diseases, including cataract, age-related macular degeneration, and Graves' ophthalmopathy; smokers are subject to more severe disease courses and less favorable treatment outcomes. Uveitis is twice as likely in smokers; smoking may also delay its resolution. Smoking and ETS exposure are major risk factors for diseases of other organs, with associated ocular complications as well, such as diabetes mellitus. ETS exposure is also associated with ocular surface pathologies, including dry eye syndrome. In children, early-life ETS exposure and maternal smoking during pregnancy are strongly associated with refractive errors and strabismus. Currently, available data on potential risks attributable to ETS exposure regarding ocular diseases are scarce and, in some instances, controversial. CONCLUSION: In addition to smoking, ETS exposure is also a significant public health concern with possible links to several ocular diseases. However, the level of education of at-risk populations in this regard does not match the strength of the evidence.

Central Serous Chorioretinopathy Risk Factors in An Iranian Cohort: A Case-control Study.

Purpose: This study aimed to investigate the possible risk factors of central serous chorioretinopathy (CSCR) in an Iranian cohort. Methods: We recruited 39 consecutive CSCR cases and 80 age-matched controls with no ocular pathology from the same medical center from March 2019 to March 2021. Enrolled patients underwent complete ophthalmological examination and extensive history taking in a referral setting. Logistic regression analysis was performed to detect any possible association of potential risk factors with CSCR. Results: The mean age of CSCR patients was 40.69±7.71 years. The male-to-female ratio in cases and controls was 1:1.79 and 1.22:1, respectively. Logistic regression analysis revealed that alcohol consumption (odds ratio, OR: 62.0, P<0.001), smoking (OR: 4.0, 95% CI: 1.47-10.85, P<0.006), corticosteroid use (OR: 6.95, 95% CI: 2.64-18.28, P<0.001), and high psychological stress (OR: 13.34, 95% CI: 4.68-38.02, P<0.01) were significant risk factors for developing CSCR. Ischemic heart disease (P=0.550), hypertension (P=0.750), and hyperopia (P=0.467) were not associated with the risk of CSCR. The most common form of steroid use was oral in both groups. No pregnant female was present in the study sample, precluding the assessment of its potential association with CSCR. Conclusion: CSCR often affects individuals of productive working ages; thus, identifying its preventable risk factors is highly encouraged. Our results suggested that alcohol consumption, smoking, and high levels of psychological stress are independent, preventable risk factors for CSCR.

The effect of vitamin D supplementation on the outcome of treatment with bevacizumab in diabetic macular edema: a randomized clinical trial.

PURPOSE: Concomitant vitamin D deficiency (VDD) is speculated to aggravate diabetic macular edema (DME). We aimed to determine the effect of hypovitaminosis D correction on the outcome of treatment with intravitreal bevacizumab (IVB) in DME eyes. METHODS: In this randomized clinical trial, 83 eyes of 83 patients with DME were recruited and divided into three groups: normal vitamin D levels + IVB administration (Group 1), vitamin D insufficient/deficient + IVB administration (Group 2), and vitamin D insufficient/deficient + IVB administration + oral vitamin D supplementation (Group 3). Participants were followed for 6 months after the intervention. Visual (corrected distance visual acuity, CDVA) and anatomical (central macular thickness, CMT) outcomes of intervention were evaluated 1, 3, and 6 months after three monthly loading doses of IVB were given. Serum vitamin D levels were measured 1 and 6 months after the third IVB administration. RESULTS: A total of 29, 26, and 28 eyes were enrolled in groups 1, 2, and 3, respectively. In months 1, 3, and 6, after the three basic loading doses of IVB, visual acuity and CMT improved in all three groups, but improvements (both functional and anatomical) in groups 1 and 3 in month 6 were more significant than in group 2 (mean CDVA LogMAR changes: - 0.18 ± 0.03, - 0.14 ± 0.05, and - 0.2 ± 0.06; mean CMT reductions: - 82.24 ± 11.43, - 66.62 ± 14.34, and - 86.14 ± 18.36, in groups 1, 2, and 3, respectively; p < 0.001). The mean number of IVB injections during follow-up was 5.33 (range 4-7), which did not differ between the groups. CONCLUSION: Correction of vitamin D deficiency in DME patients with type 2 diabetes and vitamin D deficiency, in addition to IVB injections, may play a role in improving CDVA and CMT. However, this beneficial effect seems to be delayed by several months. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20200407046978N1, registered on April 11, 2020, retrospectively registered ( https://en.irct.ir/trial/46999 ).

Evaluation of Sestrin 2, Adiponectin, AMPK, and mTOR Genes Expression in Acute Myeloid Leukemia Patients.

BACKGROUND: Effective treatment of acute myeloid leukemia (AML) is still controversial, therefore; a comprehensive understanding regarding the impaired cellular signaling pathways in AML can be useful in designing new therapeutic approaches. Among signaling pathways involved in AML, the mammalian target of rapamycin (mTOR) signaling pathway is of particular importance. While dysregulation of mTOR signaling has been reported in a wide range of patients with AML, but most studies have focused on mTOR downstream targets, and mTOR upstream targets have been overlooked. OBJECTIVE: In this study, expression of mTOR genes and three upstream targets (5' adenosine monophosphate-activated protein kinase (AMPK, adiponectin, and sestrin 2) involved in mTOR signaling was investigated. MATERIALS AND METHODS: In this study, expression of mTOR, AMPK, sestrin 2, and adiponectin genes in 60 patients with AML were evaluated compared to those of 30 healthy individuals as controls using the Real-Time polymerase chain reaction (Real-Time RT-PCR) method. RESULTS: According to the results, there was a significant difference in the expression of all the studied genes in patients in comparison to the normal control group (P <0.05). Expression of the mTOR gene was increased, while expression of AMPK, sestrin 2, and adiponectin genes was decreased in the patients with AML. Mean expression of the genes (2-ΔCt) (AMPK, sestrin 2, adiponectin, and mTOR) was equal to 7.9, 3.2, 3.74, and 1.49 for controls and 6, 2.1, 2.83, and 2.64 for patients with AML, respectively. CONCLUSIONS: Given the decreased expression levels of sestrin 2, adiponectin, and AMPK genes as tumor inhibitors and the increased expression level of the mTOR gene as an oncogene in the patients with AML in our study, it is thought that disruption of this pathway may be involved in leukemogenesis and can be considered as an effective factor in the progression of cancer.

Intravitreal connective tissue growth factor neutralizing antibody or bevacizumab alone or in combination for prevention of proliferative vitreoretinopathy in an experimental model.

Connective tissue growth factor (CTGF) is released by retinal pigment epithelial (RPE) cells and detectable in proliferative membranes (PrMs). This experimental study was performed to investigate the mRNA and protein levels of both CTGF and vascular endothelial growth factor A (VEGF-A) in a rabbit model of proliferative vitreoretinopathy (PVR). In addition, the effects of a single intravitreal injection of the safe dose of anti-CTGF or bevacizumab as monotherapy and in combination were evaluated. PVR was induced in the right eye of albino rabbits by intravitreal injection of cultured adult human RPE cells. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot analysis of CTGF and VEGF-A were performed on whole eye tissue in the PVR model versus controls at different time points. In the next step, the PVR models were assigned to five groups. The monotherapy groups received a single intravitreal injection of 0.1 ml of anti-CTGF 100 µg/ml (final concentration of 6.6 µg/ml in the vitreous) or 0.03 ml of 25 mg/ml bevacizumab. In the combined group, the abovementioned amounts of anti-CTGF and bevacizumab were injected intravitreally from separate sites in one session. No antibody injection was performed in the control group. Intravitreal injection of 0.1 ml of control IgG (1 mg/ml of isotype matched) antibody was performed in the placebo group. After 2 weeks, histologic evaluation including, trichrome staining for collagen, immunostaining by anti-alpha-smooth muscle actin for myofibroblasts, and anti-collagen type-1 antibody on paraffin embedded anterior-posterior sections was done. In addition, fundus photography was performed for clinically equivalent PVR staging. Twenty-four hours following PVR induction, CTGF mRNA and protein levels increased five- and- three-fold compared to controls, respectively (P < 0.001). VEGF-A mRNA and protein levels decreased significantly after 72 h of PVR induction compared to controls (P < 0.05). Means of PrM thickness and myofibroblast cell counts significantly decreased in the anti-CTGF group (P < 0.001 and P < 0.05, respectively). The mean area of collagen type-1 fibers of PrM in the mono- and combination therapy groups that received intravitreal anti-CTGF was significantly reduced (P < 0.001); in addition, mild PVR (stage-1 and 2) formation occurred in comparison with moderate to severe PVR (stage-4 and higher) in other groups. In conclusion, we found that intravitreal injection of CTGF neutralizing antibody resulted in a reduction in PrM thickness, collagen fibers and myofibroblast density in the PVR model. CTGF inhibition may represent a potential therapeutic target for PVR.

Photodynamic Therapy in Ocular Oncology.

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis.

Lateral rectus muscle recession and the vertical palpebral fissure height: to do or not to do inter-muscular septum dissection?

In this study, we aimed to evaluate changes of vertical palpebral fissure height (VPFH) after unilateral lateral rectus muscle recession. Twenty-five and twenty-six patients who were candidates for lateral rectus muscle recession were assigned into "with" and "without" intermuscular septum dissection study arms. The VPFH was measured at one-day before surgery and in two weeks and three months, postoperatively. Three months after surgery, significant increase of VPFH was observed in both groups (Paired t-test; P=0.005). Also, less widening of VPFH was observed in "with intermuscular septum dissection" group (Change in VPFH in "with intermuscular septum dissection" vs "without intermuscular septum dissection" groups: 0.48 mm vs 1.34 mm; ANCOVA test; P<0.001). However, such results were not observed two weeks post-operatively (Change in VPFH in "with intermuscular septum dissection" vs "without intermuscular septum dissection" groups: -0.28 mm vs 0.28 mm; ANCOVA test; P=0.302). Intermuscular septum dissection is recommended in lateral rectus muscle recession to partially prevent the undesirable increment of VPFH.

Orbital invasion of ameloblastoma: A systematic review apropos of a rare entity.

PURPOSE: Ameloblastoma is a non-encapsulated and slow-growing tumor with high recurrence rate. Orbital involvement by this neoplasm is an extremely rare entity. In this study, we present a systematic review on this situation along with clinical and paraclinical features of a case. METHODS: An electronic search was conducted on major medical sources. Data of the cases in the literature in addition to our own case were extracted, summarized, and statistically analyzed. RESULTS: A total of 36 other cases from 20 relevant studies were also reviewed. Review topics included epidemiology, clinical presentation, pathologic features, differential diagnosis, imaging, treatment, and prognosis. We provided a five-year history of a 50-year-old man with orbital/skull base invasion of plexiform maxillary ameloblastoma. CONCLUSIONS: Maxillary ameloblastoma is a locally aggressive neoplasm, and physicians must be alert to the biologic behavior of this tumor to detect any invasion to critical structures such as orbit and cranium. Orbital ameloblastoma causes significant morbidity and mortality. We advocate meticulous patient follow-up with regular clinical examinations and paraclinical work-up for timely detection of any invasion or recurrence. The best must be done to avoid extensions by aggressive removal of maxillary ameloblastoma.

Hyperimmunoglobulin E syndrome: Genetics, immunopathogenesis, clinical findings, and treatment modalities.

The hyperimmunoglobulin E syndromes (HIESs) are very rare immunodeficiency syndromes with multisystem involvement, including immune system, skeleton, connective tissue, and dentition. HIES are characterized by the classic triad of high serum levels of immunoglobulin E (IgE), recurrent staphylococcal cold skin abscess, and recurrent pneumonia with pneumatocele formation. Most cases of HIES are sporadic although can be inherited as autosomal dominant and autosomal recessive traits. A fundamental immunologic defect in HIES is not clearly elucidated but abnormal neutrophil chemotaxis due to decreased production or secretion of interferon γ has main role in the immunopathogenesis of syndrome, also distorted Th1/Th2 cytokine profile toward a Th2 bias contributes to the impaired cellular immunity and a specific pattern of infection susceptibility as well as atopic-allergic constitution of syndrome. The ophthalmic manifestations of this disorder include conjunctivitis, keratitis, spontaneous corneal perforation, recurrent giant chalazia, extensive xanthelasma, tumors of the eyelid, strabismus, and bilateral keratoconus. The diagnosis of HIES is inconclusive, dependent on the evolution of a constellation of complex multisystemic symptoms and signs which develop over the years. Until time, no treatment modality is curative for basic defect in HIES, in terms of cytokines/chemokines derangement. Of note, bone marrow transplant and a monoclonal anti-IgE (omalizumab) are hoped to be successful treatment in future.

Femtosecond laser arcuate keratotomy for the correction of postkeratoplasty high astigmatism in keratoconus.

BACKGROUND: Astigmatism is the leading complication in visual recovery after penetrating keratoplasty (PKP) and deep anterior lamellar keratoplasty (DALK); in this study, we evaluated the outcome of femtosecond laser arcuate keratotomy (FLAK) after DALK and PKP in Iranian keratoconic patients. MATERIALS AND METHODS: In this prospective interventional case series, refractive and keratometric predictability, efficacy, and complications of FLAK for postkeratoplasty astigmatism in keratoconus were evaluated; 23 eyes of 23 consecutive patients (mean age of 32.43 ± 9.11 years) with high astigmatism were enrolled. The femtosecond laser performed paired 90°-angled arcuate incisions. RESULTS: Mean logarithm of the minimum angle of resolution of corrected and uncorrected visual acuity improved from preoperative values of 0.30 ± 0.18 and 0.85 ± 0.32 to 6-month values of 0.19 ± 0.17 and 0.65 ± 0.33, respectively (P < 0.05). Mean subjective astigmatism was 7.79 ± 2.64 diopter (D) preoperatively and 3.69 ± 2.25D at 6-month after surgery (P < 0.05). Surgically induced astigmatism was 9.27 ± 5.00D. Mean refractive spherical equivalent showed no significant (P = 0.69) hyperopic shift from - 4.21 ± 4.84D preoperatively to - 2.16 ± 6.09D postoperatively. Two (8.7%) microperforations were observed. CONCLUSION: FLAK is a relatively safe and effective method for the treatment of postkeratoplasty astigmatism.

Presentation of massive orbital hidrocystoma at birth: case report and review of the literature.

BACKGROUND: Hidrocystoma, or sudoriferous cyst, is an eyelid tumor originating from apocrine or eccrine sweat glands. Its presence in the orbit is relatively rare. CASE PRESENTATION: A full-term female child with severe right eye extrusion was referred to our department two hours after birth. We performed cyst aspiration under ultrasonic guidance; 15 cc straw-colored fluid was obtained and proptosis resolved significantly. Orbital magnetic resonance imaging (MRI) showed a large unilocular retrobulbar mass with hypo-intensity in T1 and hyper-intensity in T2. The case underwent further daily ocular assessment until day 5; when proptosis began to worsen again. On day 6, under general anesthesia, we performed aspiration and then the cyst was completely removed with an intact wall through a trans-conjunctival incision. The diameter of the aspirated cyst was about 4 cm. In pathologic consultation, a cystic cavity lined by a layer of sweat duct like epithelium with apical snouts consistent with the diagnosis of apocrine hidrocystoma was reported. CONCLUSION: To date, in the literature, six other cases of orbital hidrocystoma have been reported in childhood with protean clinical pictures; none of which presented at birth. Herein, we introduce the first case report at birth and also provide a review on the literature. Our report strongly argues against the well reputed theory of traumatic origin for orbital hidrocystoma; it has been postulated that this tumor may be the result of sweat gland cells implantation through the orbit. We thereby suggest the possible presence of choristomatous ectopic sweat gland cells in the orbit during embryogenesis.

Comparison of Scheimpflug and swept-source anterior segment optical coherence tomography in normal and keratoconus eyes.

PURPOSE: The purpose of the study was to assess the agreement of anterior segment optical coherence tomography with its older well-known opponent i.e., Sheimpflug imaging in evaluation of the cornea in normal and keratoconus subjects. METHODS: 107 normal and 56 keratoconus eyes were evaluated with the anterior segment optical coherence tomography followed by the Scheimpflug imaging. Parameters included axial keratometry data in both of steep and flat meridians, mean keratometry and the astigmatism values in the central 4.0 mm zone, central, thinnest and apex corneal thicknesses, Q-value in 8 mm zone and pupil diameter. Corneal topographic maps were recorded and were evaluated for anterior highest and lowest points, posterior highest and lowest points. Average values were recorded for analysis. RESULTS: All anterior cornea keratometry indices showed perfect agreement between two devices in normal corneas; while the level of agreement in keratoconus cases ranged from moderate to strong. All posterior keratometry indices also showed perfect agreement in both groups; except for flat K in normal corneas and steep K in KC ones. The amount of corneal cylinder in normal corneas had perfect agreement, and moderate to strong agreement in anterior/posterior cornea in keratoconus group. Anterior highest and lowest points showed strong and perfect agreement in normal and keratoconus cases, respectively. Posterior highest and lowest points showed strong agreement in normal cases. Thickness indices (central, thinnest, and apex thicknesses) showed perfect agreement between two devices in both normal and KC groups. Mean values of anterior and posterior highest points were statistically higher in Scheimpflug system. CONCLUSIONS: Although two imaging technologies had statistically numerical different output, it seems that they have a good agreement in most parameters.

Intravitreal Diclofenac plus Bevacizumab versus Bevacizumab alone in treatment-naive diabetic macular edema: a randomized double-blind clinical trial.

The aim of this study is to evaluate the short-term effects of a single intravitreal injection of 1.25 mg Bevacizumab combined with 300 lg/0.1 mL Diclofenac (IVB/D) versus 1.25 mg intravitreal Bevacizumab (IVB) alone in the treatment of naive diabetic macular edema (DME). In this prospective, randomized clinical trial, 80 eyes were included in the final analysis; 42 and 38 of which in the IVB and IVB/D groups, respectively. The primary outcome measure was a change in best-corrected visual acuity (BCVA) in logMAR at week 4. The secondary outcomes included changes in central macular thickness (CMT), macular volume, and potential injection-related complications. Significant improvement of BCVA was demonstrated in both study arms (mean reductions in LogMAR: -0.088 ± 0.278, -0.228 ± 0.330 for IVB and IVB/D, respectively). The difference in BCVA changes was in favor of IVB/D; however, not to a statistically significant level (P = 0.160). Significant reduction of CMT was documented in both study arms (mean reductions: 82.43 ± 160.09 and 153.26 ± 163.85 for IVB and IVB + IVD, respectively). Comparison of CMT changes between groups showed that IVB/D reduced CMT more than that of IVB (P = 0.04). Effects on macular volume corresponded to those of CMT. No injection-related complications or significant alterations in intraocular pressure were observed in any of the study arms. In treatment-naive DME, superiority of IVB/D combination therapy over IVB monotherapy may exist; especially as regards anatomical features. In our therapeutic arsenal for DME, IVD can be added as an adjunct to Bevacizumab.

Effects of Corneal Collagen Crosslinking on Confocal Microscopic Findings and Tear Indices in Patients with Progressive Keratoconus.

BACKGROUND: To evaluate any change in tear indices and confocal microscopic findings after corneal collagen crosslinking (CXL) in patients with progressive keratoconus. METHODS: Thirty-two consecutive eyes from 23 patients having progressive keratoconus were enrolled in this prospective, interventional cohort study. The standard crosslinking surgery was performed for all patients. Visual, refractive, and topographic evaluations were done before and at 6 months after surgery. Tear function tests and confocal microscopic examination were performed before and at 1 month and 6 months after the procedure. RESULTS: There was no significant change in Schirmer-1 test results and tear osmolarity at 1 month and 6 months after CXL. Using confocal microscopy, all eyes showed reduced or absent subepithelial nerve plexus. Differences in basal epithelial cell density, epithelial mean cell area, and keratocyte density in anterior and middle stroma and endothelial cell pleomorphism were all significant at 1 month and 6 months after CXL (P < 0.05). No significant change was noted in endothelial cell count and their polymegathism at 6 months follow-up. Significant improvement was noted in uncorrected visual acuity, best corrected visual acuity, flattest corneal meridian (K2), and maximum keratometry in Pentacam (Kmax) after 6 months of the procedure. CONCLUSIONS: While CXL would have no effect on tear indices and endothelial cell count, it can cause a significant reduction in subepithelial nerve plexus and significant alterations in epithelial cell density in the anterior and middle stroma.

Pentacam topographic changes after collagen cross-linking in patients with keratoconus.

BACKGROUND: Corneal cross-linking (CXL) with riboflavin and ultra-violet A is less invasive in comparison with other procedures such as penetrating keratoplasty. Hence, we planned this study to evaluate the efficacy of CXL in disease progression and to compare keratoconus indices before and 1 year after cross-linking by Pentacam. MATERIALS AND METHODS: In this prospective clinical trial, we enrolled 37 eyes of 37 patients suffering from keratoconus who were candidates for CXL. All eyes were examined before and one 1 year after surgery with a slit lamp and Pentacam for corneal topography. To compare the mean of each Pentacam parameter and index before and 1 year after the surgery, we used paired t-test. RESULTS: There were 23 males and 14 females. The mean age was 21.5 years 18-30 years). At the 12(th) month examination, the corneal thickness had decreased (P = 0.0068) and the Index of Height Decentration (IHD) had increased (P = 0.016). There were no statistically significant differences in other indices and parameters 1 year after CXL. CONCLUSION: Most of the parameters and indices had not changed during 1 year after CXL. The procedure seems to be effective in stopping the disease progression at least for 12 months after surgery.

Comparison of the performance of the updated Schwartz, combined Schwartz and the Grubb glomerular filtration rate equations in a general pediatric population.

To determine the performance of the updated Schwartz, combined Schwartz and Grubb glomerular filtration rate (GFR) equations in a relatively large number of healthy children with no known renal disease, we studied 712 students aged between seven and 18 years from the Isfahan province of Iran by random cluster sampling between 2009 and 2010. Blood investigations included blood urea nitrogen, creatinine and cystatin C. For each participant, GFR was calculated based on the three equations. We used Bland-Altman plots and weighted kappa statistics to compare the performance of the study equations. The mean age of the children was 12.2 ± 2.4 years. A high concordance in estimating GFR (mean difference: 0 ± 12.7 mL/min/1.73 m 2 ) and a very good agreement in defining chronic kidney disease (CKD) and non-CKD individuals (weighted kappa: 0.85; 95% confidence intervals: 0.69-1) were observed between the updated Schwartz and the combined Schwartz equations. Poor agreement was observed between the Grubb equation and two Schwartz equations in estimating GFR and defining CKD. There was no systematic deviation between the updated Schwartz and the combined Schwartz equations in children with normal renal function. The Grubb equation was highly inconsistent with both Schwartz equations in this population. We conclude that the updated Schwartz equation is simpler and more accessible than the combined Schwartz equation in daily clinical practice and CKD screening programs.