Histopathology and electron microscopy evaluation of the sildenafil effect on diabetic rats' retinae.

PURPOSE: Although there is increasing evidence that phosphodiesterase-5 (PDE-5) inhibitors modify the effect of diabetes on different tissues, its effect on diabetic retinopathy is not well studied. METHODS: Forty male Sprague-Dawley (SD) rats were divided into four groups: group I = control group that received no treatment; group II (diabetic group), in which diabetes was induced by a single streptozotocin injection; group III (sildenafil small dose, SSD), in which diabetes was similarly introduced (however, rats received daily oral 1 mg/kg sildenafil citrate (SC) for 3 months); and group IV (sildenafil large dose, SLD), which was as in group 3, but SC was 2.5 mg/kg. After 3 months, globes were removed and retinae were dissected; one globe from each rat was examined by light microscopy (LM), and the other by electron microscopy (EM). RESULTS: In contrast to the control group, diabetic rats in group II demonstrated well-established diabetic changes in the form of capillary congestion, decreased cell population, hyaline changes of capillary walls, and degenerated nerve fiber layer by LM. Similarly, EM demonstrated photoreceptor degeneration, mitochondrial cristolysis, and vacuolated depleted cells among other features in group II. These diabetic features were less prominent in group III and nearly absent in group IV. CONCLUSION: SC use in the early stages of DR may prevent/delay diabetic retinopathy development or progression in diabetic rat models, an effect that seems to be dose-related.

Chronic sildenafil citrate use decreases retinal vascular endothelial growth factor expression in diabetic rats: a pilot study.

BACKGROUND: Sildenafil citrate (SC) attenuates endothelial dysfunction. However, its effects on diabetic retinopathy (DR), which is mainly a microvascular disease, remain unclear. Vascular endothelial growth factor (VEGF) is known to be a critical mediator of DR. Therefore, we investigated the effects of SC on diabetic retina by measuring VEGF levels. METHODS: In this study, twenty-eight rats were divided into the following groups: group I, the control group; group II, rats with streptozotocin-induced diabetes; group III, rats with streptozotocin-induced diabetes receiving daily oral sildenafil at 1 mg/kg; and group IV, rats with streptozotocin-induced diabetes receiving high-dose daily sildenafil at 2.5 mg/kg. After 3 months, VEGF was measured in the retina specimen in one eye and the vitreous body in the other eye by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. RESULTS: We found that VEGF expression in the retina was low in all rats from groups I and IV and in 30% of rats from group III; 80% of rats in group II demonstrated high VEGF expression in the retinae (P < 0.001). VEGF concentrations in the vitreous body samples were 32 ± 2, 61 ± 4, 44 ± 5, and 36 ± 3 pg/l in groups I-IV, respectively (P < 0.001). CONCLUSION: VEGF decreased significantly in the eyes of diabetic rats after chronic oral sildenafil citrate treatment. SC may have a modifying/attenuating effect on DR. However, further studies are needed to evaluate its use as an adjunctive treatment.

Orbital Complications of Chronic Rhinosinusitis: Two Years' Experience in a Tertiary Referral Hospital.

PURPOSE: To investigate the different clinical manifestations in Egyptian patients with orbital complications of rhinosinusitis (RS) according to the pathology within the paranasal sinuses. METHODS: The medical records of patients presented with chronic RS between August 2018 and December 2020 were retrospectively reviewed. RESULTS: This study included 64 patients: 28 patients with subperiosteal abscess (SPA), 10 with allergic fungal RS, 6 with isolated fungal RS, 6 with invasive fungal RS, and 14 with mucocele. The most common manifestation was proptosis, limitation of ocular motility, periorbital swelling, and pain. A relative afferent pupillary defect was present in all cases of invasive fungal sinusitis. Surgical interventions were performed in 63 out of 64 cases. All the ophthalmological manifestations were reversible except for patients with invasive fungal rhinosinusitis. CONCLUSION: Orbital complications of RS may require early surgical intervention with multidisciplinary counseling between ophthalmologists, otorhinolaryngologists, radiologists, and neurologists.

Orbital Complications of Acute Invasive Fungal Rhinosinusitis: A New Challenge in the COVID-19 Convalescent Patients.

Purpose: Increased incidence of acute invasive fungal rhinosinusitis (AIFR) in the setting of COVID-19 is undeniable. This can be attributed to its effect on innate immunity and extensive use of corticosteroids. The goal of our study was to assess the orbital complications of AIFR and its management in the COVID-19 convalescent patients. Methods: Our longitudinal prospective study included 45 patients with orbital complications of AIFR in recently recovered COVID-19 patients. We performed otorhinolaryngological, ophthalmological, and neurological examinations to monitor the manifestations of the disease. Computed tomography and contrast enhanced magnetic resonance imaging were performed to detect the extent of infection. Antifungal medications, surgical intervention, and general condition management were all provided to all the patients. Results: We reported pre-septal cellulitis, orbital cellulitis, and orbital apex syndrome in 18, 13, and 10 patients, respectively. Four patients had cavernous sinus thrombosis. Mucormycosis and Aspergillus species were detected in 80% and 11.11% of our patients, respectively, while the mixed infection was found in 8.88% of our patients. Diabetes mellitus was the most common cause of immunocompromise (95.55% of our patients). Orbital pain and ophthalmoplegia were the most common ocular manifestations, followed by proptosis and relative afferent pupillary defect. All patients underwent surgical intervention, except for one patient who was unfit for surgery. One patient had orbital exenteration. The ophthalmological manifestations were reversible in cases of orbital and pre-septal cellulitis. The overall survival rate was 66.67%. Conclusion: Early diagnosis and treatment of AIFR can decrease the morbidity and mortality rate of affected patients.

Accuracy of a universal theoretical formula for power calculation in pediatric intraocular lens implantation.

PURPOSE: To compare the accuracy of Barrett Universal II formula with other formulas (Holladay 2, Hoffer Q, and SRK/T formulas) in the prediction of postoperative refraction for pediatric intraocular lens implantation. SETTING: Academic medical center/children's hospital, San Francisco, California. DESIGN: Retrospective case series. METHODS: Children aged 16 years or younger who underwent cataract extraction and IOL implantation (2012 to 2019) and had refraction assessed at 3 to 16 weeks postoperatively were included. Prediction error (PE) was calculated as postoperative mean spherical equivalent minus the target refraction. Mean, median, and standard deviation was calculated for PE and absolute PE. Performance across covariables (axial length, age, biometry type, keratometry, etc.) was studied, and a multivariate regression analysis was performed using a single prediction model for each formula. RESULTS: Sixty-four eyes of 64 patients, aged 1.5 to 15.5 years, were included. Barrett Universal II formula had the lowest mean PE (-0.22 diopters [D]), SD (1.18 D), median PE (-0.26 D), and median absolute PE (0.71) compared with those of the other formulas. Holladay 2 formula performed similarly to Barrett Universal II formula, and SRK/T formula had the greatest mean PE (-0.50 D) and SD (1.22 D). Barrett Universal II formula predictions were stable across all variables. CONCLUSIONS: Barrett Universal II formula demonstrated similar or superior performance when compared with other formulas in this pediatric study. Holladay 2 formula performed similarly to Barrett Universal II formula, and SRK/T formula had the least reliable performance, across several key biometric characteristics. Although PEs can be highly variable in pediatric populations, this study supports Barrett Universal II formula as a reasonable and reliable option for lens power calculation in children, including those with extreme biometric measurements.

Lateral Rectus Muscle Tendon Elongation by an Auto Graft from the Resected Medial Rectus Muscle as a Monocular Surgery for Large-Angle Sensory Exotropia.

PURPOSE: To evaluate using the resected medial rectus muscle for elongation of the lateral rectus tendon in monocular surgery for large-angle sensory exotropia. PATIENTS AND METHODS: A prospective case series was carried out in Tanta University hospital from January 2017 to June 2018 including 16 patients with large-angle sensory exotropia ≥50PD. The near and distance angles of exotropia were measured; any restrictions in adduction or abduction were recorded and scaled from -4 to 0. Resection of the medial rectus muscle was done first; the resected segment was attached to the lateral rectus muscle after dissection by mattress sutures, and the muscle was recessed after elongation according to the preoperative distance angles. Successful motor alignment was considered if the angle measurement was within 10 PD of orthotropia at distance after 6 months. The stability of the alignment, any motility restrictions, and patient satisfaction were recorded at each follow-up visit until the 6th month. RESULTS: The mean age of the study patients was 30.68±13.30 years. The best-corrected visual acuity of the exotropic eyes by logMAR was 1.2±0.3; the mean of the preoperative distance angle of deviation was -72.19 ±14.26 PD. The mean preoperative adduction and abduction restrictions were -1.19 ±1.52 and -1.13 ±1.09, respectively. There was significant improvement in the distance angle of deviation at the last follow-up after 6 months (p=0.001*). Also, there was improvement in both adduction and abduction restriction from the first to last follow-up. Thirteen patients (81.2%) were satisfied at the 6-month follow-up. CONCLUSION: Elongation of the lateral rectus muscle by an autograft from the resected medial rectus muscle is an easy, effective procedure for large-angle sensory exotropia. Patients achieve good postoperative alignment with minimal restriction of ocular motility.

Contrast-Enhanced Ultrasound with VEGFR2-Targeted Microbubbles for Monitoring Regorafenib Therapy Effects in Experimental Colorectal Adenocarcinomas in Rats with DCE-MRI and Immunohistochemical Validation.

OBJECTIVES: To investigate contrast-enhanced ultrasound (CEUS) with VEGFR2-targeted microbubbles for monitoring therapy effects of regorafenib on experimental colon carcinomas in rats with correlation to dynamic contrast-enhanced MRI (DCE-MRI) and immunohistochemistry. MATERIALS AND METHODS: Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n = 21 (n = 11 therapy group; n = 10 control group) female athymic nude rats (Hsd: RH-Foxn1rnu). Animals were imaged at baseline and after a one-week daily treatment with regorafenib or a placebo (10 mg/kg bodyweight), using CEUS with VEGFR2-targeted microbubbles and DCE-MRI. In CEUS tumor perfusion was assessed during an early vascular phase (wash-in area under the curve = WiAUC) and VEGFR2-specific binding during a late molecular phase (signal intensity after 8 (SI8min) and 10 minutes (SI10min)), using a conventional 15L8 linear transducer (transmit frequency 7 MHz, dynamic range 80 dB, depth 25 mm). In DCE-MRI functional parameters plasma flow (PF) and plasma volume (PV) were quantified. For validation purposes, CEUS parameters were correlated with DCE-MRI parameters and immunohistochemical VEGFR2, CD31, Ki-67 and TUNEL stainings. RESULTS: CEUS perfusion parameter WiAUC decreased significantly (116,989 ± 77,048 a.u. to 30,076 ± 27,095a.u.; p = 0.005) under therapy with no significant changes (133,932 ± 65,960 a.u. to 84,316 ± 74,144 a.u.; p = 0.093) in the control group. In the therapy group, the amount of bound microbubbles in the late phase was significantly lower in the therapy than in the control group on day 7 (SI8min: 283 ± 191 vs. 802 ± 460 a.u.; p = 0.006); SI10min: 226 ± 149 vs. 645 ± 461 a.u.; p = 0.009). PF and PV decreased significantly (PF: 147 ± 58 mL/100 mL/min to 71 ± 15 mL/100 mL/min; p = 0.003; PV: 13 ± 3% to 9 ± 4%; p = 0.040) in the therapy group. Immunohistochemistry revealed significantly fewer VEGFR2 (7.2 ± 1.8 vs. 17.8 ± 4.6; p < 0.001), CD31 (8.1 ± 3.0 vs. 20.8 ± 5.7; p < 0.001) and Ki-67 (318.7 ± 94.0 vs. 468.0 ± 133.8; p = 0.004) and significantly more TUNEL (672.7 ± 194.0 vs. 357.6 ± 192.0; p = 0.003) positive cells in the therapy group. CEUS parameters showed significant (p < 0.05) correlations to DCE-MRI parameters and immunohistochemistry. CONCLUSIONS: CEUS with VEGFR2-targeted microbubbles allowed for monitoring regorafenib functional and molecular therapy effects on experimental colorectal adenocarcinomas with a significant decline of CEUS and DCE-MRI perfusion parameters as well as a significant reduction of specifically bound microbubbles under therapy, consistent with a reduced expression of VEGFR2.

Ocular axial growth in pseudophakic eyes of patients operated for monocular infantile cataract: a comparison of operated and fellow eyes measured at surgery and 5 or more years later.

PURPOSE: To report the change in axial length (AL) over time and to compare the percentage of AL growth of pseudophakic eyes operated on for monocular cataract to that of the unoperated fellow eyes. METHODS: The medical records of children operated on by a single surgeon for monocular congenital cataract before 7 months of age were retrospectively reviewed. Inclusion criteria were corneal diameter of ≥9 mm and availability of AL data for >5 years' follow-up after cataract surgery and >1 year after IOL implantation (in case of secondary IOL). Cataract with persistent fetal vasculature causing stretching of the ciliary processes, diagnosis of glaucoma or glaucoma suspect, and eyes with aphakia were excluded. Globe AL was measured by immersion ultrasound at surgery and 5 or more years later. RESULTS: A total of 24 children were identified. Average age at cataract surgery was 2.6 ± 2.1 months. Age at last follow-up was 8.4 ± 2.8 years and duration of follow-up was 8.2 ± 2.8 years. 13 eyes received a primary IOL and 11 eyes received a secondary IOL. AL was significantly different between operative and fellow eyes, preoperatively (18.1 mm vs 18.7 mm, P = 0.004), and at the final follow-up (22.2 mm vs 23.0 mm, P = 0.03). Differences in AL growth of operated and fellow eyes were not significant (4.1 mm vs 4.4 mm, P = 0.4). Similarly, percentage of AL growth of operated and fellow eyes was also not significantly different (23% vs 23.6%, P = 0.7). CONCLUSIONS: Eyes operated for monocular cataract have similar axial growth to that of fellow unoperated eyes, despite having a shorter AL at the time of surgery.

Primary versus secondary IOL implantation following removal of infantile unilateral congenital cataract: outcomes after at least 5 years.

PURPOSE: To report outcomes after at least 5 years' follow-up of consecutive patients at a single center undergoing unilateral congenital cataract surgery during infancy with primary intraocular lens (IOL) implantation at the time of surgery or undergoing secondary IOL implantation later in childhood. METHODS: The medical records of pseudophakic children who received initial cataract surgery before 7 months of age were retrospectively reviewed. Children with acquired cataract, persistent fetal vasculature, congenital glaucoma, or follow-up of <5 years were excluded. RESULTS: Mean age at time of cataract surgery was 2.7 months in the primary group (n = 13) and 1.9 months in the secondary group (n = 13). Mean age at IOL implantation in the latter group was 4.9 ± 2.2 years. Mean age at final follow-up was 10.7 ± 4.2 years in the primary group and 8.7 ± 3.0 years in the secondary group. Glaucoma surgery was performed in 2 primary group eyes and 1 secondary group eye; it was medically controlled in 2 additional eyes of the latter group. One secondary group eye was diagnosed as glaucoma suspect. Visual axis opacification required surgery in 5 primary group eyes and 2 secondary group eyes before IOL implantation. Unplanned IOL exchange or removal for high myopia was required in 3 primary group eyes and 1 secondary group eye. Strabismus surgery was performed in 3 primary group eyes and 7 secondary group eyes. Median visual acuity at final follow-up was 20/150 in both groups. Refraction at last follow-up was -2.9 ± 3.3 D in the primary and -1.8 ± 2.5 D in the secondary group. CONCLUSIONS: Reoperations were common in both groups over long-term follow-up. Close monitoring for glaucoma is also needed in both groups.