Medical hypothesis discovery and innovation in ophthalmology

Advanced Keratoconus and ectatic corneal diseases may lead to corneal thinning and irregular astigmatism. The optical distortion caused by these pathologies may result in poor visibility for the surgeon during phacoemulsification operations. Thus, the risk of complication would be increased intraoperatively (capsular rupture, vitreous loss). The aim of this case series was to use Rigid Gas Permeable (RGP) contact lens to improve visualization during all the stages of phacoemulsification surgery in irregular corneas and to avoid open sky technique for cataract removal during penetrating keratoplasty. A customized, 12 mm, RGP contact lens was designed and manufactured. Two peripheral notches were customized to fit the hand position of the surgeon (at 11 O’clock and 2 Clock in this case series) to allow clear corneal incisions. Six eyes of 6 patients were included (3 eyes with advanced keratoconus and a severely optically distorted, yet clear corneas, planned for penetrating keratoplasty on the same day; 2 eyes were status post-intracorneal ring segment implantation for stage 4 keratoconus and 1 eye had combined phacoemulsification with superficial keratectomy to remove paracentral corneal Salzmann nodule). Lens opacities ranged from +2 to +4 nuclear sclerosis in all eyes. Good visualization of the anterior lens and capsule attained with the RGP contact lens fitting. Improved visualization was reported during all the steps (Capsulorhexis, IA, Phaco. IOL implantation). The phacoemulsification was smooth and non-complicated in a total of 6 eyes of 6 patients. In these cases, without RGP fitting, the operation was not technically possible. The customized notches allowed any insertion of surgical instruments, and with the help of viscoelastic maintained a good stability of the contact lens during the operation. We concluded that customized method Rigid Gas Permeable contact lens, may help reducing complications during phacoemulsification in advanced corneal ectasia and perhaps in irregular corneas as well.

Exudative age related macular degeneration (AMD) is related to active choroidal neovascularization (CNV) and formation of disciform scars. Vascular endothelial growth factor (VEGF) mediated choroidal vascular endothelial cell (CVECs) proliferation is characteristic of CNV. Intravitreal injections of bevacizumab, ranibizumab and aflibercept (anti-VEGF monoclonal antibodies) are used to treat exudative AMD. Pazopanib, a tyrosine kinase inhibitor, inhibits neovascularization through blockade of intracellular tyrosine kinase VEGF receptor and platelet-derived growth factor receptor. In this in vitro investigation, we evaluated the inhibitory consequences of escalating doses of pazopanib on proliferation of VEGF-enriched CVECs to establish a safe dosage range. VEGF (50 ng/mL) enriched CVECs were treated with escalating doses of pazopanib (10, 50,100 and 250 µM). Cell proliferation rates (WST-1 assay), cell viability (trypan blue exclusion assay), and reactive oxygen species (ROS) levels were measured at 48h, 72h and 1 week. Intracellular caspase 3 levels and morphological changes were recorded. VEGF enriched CVECs showed a significant decrease in cell proliferation rates after one week of treatment with increasing doses of pazopanib (10, 50,100 and 250 µM) treatment i.e. 87.8%, 43.0%, 38.1% and 9.3% compared to controls (p<0.001). Similarly, trypan blue exclusion assay revealed a decrease in cell viability as 81.8%, 81.0%, 53.4% and 8.7%, respectively (p<0.05). Further, pazopanib actively inhibited proliferation of VEGF-enriched CVECs, with 1.32, 1.92, 1.92 and 4.1-fold increase (p<0.01) in intracellular caspase 3 levels. VEGF-enriched CVECs treated with escalating doses of pazopanib decreased cell viability and increased caspase 3 levels in a time and dose dependent manner.

Descemet’s stripping automated endothelial keratoplasty (DSAEK) is a surgical technique for corneal transplantation in case of corneal decompensation. One of the main complications is graft detachment (GD) recoverable with Air Re-bubbling (ARB). The aim of this retrospective, interventional case series was to identify factors related to this complication in eyes operated for bullous keratopathy (BK) and Fuchs dystrophy (FD). We considered one-hundred patients who underwent DSAEK for BK or FD between January 2016 and October 2017 at Department of Ophthalmology, Policlinico Universitario of Bari, Italy. Studied parameters included physiological and pathological anamnesis of both donors and recipients and properties of donor lenticules and of the recipient corneas. Data was analyzed using One-way ANOVA with Tukey post hoc test and Chi-square test with Odds Ratio (OR) calculation. We grouped patients according to diagnosis. GD occurred in 9 eyes affected by BK and 19 by FD (p=0.003, OR = 0.25, 95% CI, 0.098-0.62). It was recovered with ARB. In BK, ARB correlated to complicated cataract extraction (p=0.04, OR = 7.83, 95% CI, 1.28 - 47.98) and aphakia (p=0.026, OR = 54.38, 95% CI, 2.51 - 11.76). In FD, ARB was associated to donor death for neoplasia (p=0.06, OR= 4.04, 95% CI, 1.06 - 15.37). No other differences were found. In conclusion, we could hypothesize that in FD patients, donor cancer therapy may play a role on altered corneal fibroblast metabolism, activating a synergetic effect between chemotherapy and genetic alteration of FD, which may lead to an altered adhesion of donor lenticule on recipient's stroma. In BK patients, complicated cataract extraction and aphakic status of recipient eye may contribute to altered adhesion of donor lenticule post-DSAEK.

Bilateral limbal stem cell deficiency (LSCD) treatment requires the need to obtain allogenic limbal tissue for transplantation. Outcomes of different surgical techniques depend on multiple factors, including the underlying etiology, ocular surface, eyelid status and used surgical intervention. Some of the management options for bilateral LSCD include cadaveric, living related or living non-related conjunctival limbal allograft (CLAL), keratolimbal allograft (KLAL), allogenic cultured limbal epithelial transplantation (CLET) and allogenic simple limbal epithelial transplantation (SLET). Systemic immunosuppressive therapy plays a pivotal role in survival of transplanted tissue. The present review focuses on different systemic immunosuppression protocols for limbal allograft and allogenic limbal epithelial cell transplantation, with specific emphasis on different surgical techniques and their outcomes. We included all reports with details of different systemic immunosuppression protocols for limbal allograft and allogenic limbal epithelial cell transplantation. Oral cyclosporine A at different doses is the most commonly used immunosuppressive agent in limbal allograft and allogenic limbal epithelial cell transplantation. However, different studies using oral mycophenolate mofetil and tacrolimus also reported good results. In conclusion, systemic immunosuppression protocols for limbal allograft and allogenic limbal epithelial cell transplantation are not standardized. Further studies regarding different surgical techniques should assess outcomes and adverse effects of such protocols.

Though microaneurysms are the hallmark of diabetic retinopathy (DR), large aneurismal changes termed as ''macroaneurysms'' (MAs) may also occur in the course of chronic diabetic macular edema. MAs are usually accompanied by intraretinal hard exudates, fluid accumulation and retinal hemorrhages. Detection of MAs is clinically important as it implies that macular edema is usually chronic and therefore can be resistant to intravitreal anti-vascular endothelial growth factor injections. Multimodal imaging consisting of fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT) or OCT-angiography (OCTA) can be performed to detect and understand the nature of MA and thereby select proper treatment modality. Herein, we report multimodal imaging features of a 64-year-old woman with insulin-dependent diabetes mellitus presented with treatment naive severe macular edema and a macroaneurysm at the right temporal macula. In conclusion, FA, ICGA and OCT seem to be far superior to OCTA to detect these lesions due to probable slow flow inside the MA.

Our aim was to review clinical outcome and patient satisfaction after cataract surgery to obtain spectacle independence following multifocal intraocular lens (IOL) implantation. A prospective case-series study was designed to evaluate the safety and efficacy of the Hanita FullRange pseudophakic multifocal intraocular lens in patients with programmed cataract surgery, performed between October 2017 and May 2018, with follow-up after 12 months. Manifest refraction spherical equivalent (SE), SE refractive accuracy, uncorrected distance (UDVA), intermediate (UIVA) and near visual acuity (UNVA) and a binocular defocus curve were evaluated. In addition, a short satisfaction questionnaire was developed. Surgeries were performed without viscoelastic substance. The corneal endothelial cell density (ECD), central corneal thickness (CCT), and intraocular pressure (IOP) were also evaluated. A total of 480 eyes of 240 patients with a mean ± standard deviation (SD) of age of 75 ± 6.12 years were included. The mean ± standard deviation (SD) of preoperative SE was 2.0 ± 2.18 D (range; -5.50 to 4.75) which decreased to -0.04 ± 0.28 D (range; -0.75 to 0.625) 12 months after surgery. Regarding SE refractive accuracy 82.9 % of eyes obtained SE values between -0.25 and 0.25 D. There was no loss of lines of vision and 98.3% of patients achieved UDVA between 20/20 and 20/25. The UNVA (binocular) obtained was J1 for 72.5% and J2 for 27.5% of patients. Regarding defocus curve, 0.04 logMAR for -3.0 D, 0.09 logMAR for -1.5 D and 0.03 logMAR for 0 D was achieved. The mean CCT was increased by 6.62 ± 2.79 micrometers (1.24%), the mean ECD was decreased by 226.08 ± 11.63 cell/mm2 (9.00 %) and the IOP remained stable one year after surgery. In response to the satisfaction questionnaire, 92% of patients stated that they had obtained spectacle independence. Finally, spectacle independence was achieved in most of the cases, with a high level of patient satisfaction one year after implantation of a FullRange IOL. No complications were detected. We concluded that the refractive efficacy of FullRange multifocal IOL was proved in majority of cases. A large follow up period is necessary in future studies to confirm the results.

The purpose of this study was to compare the effects of propranolol, timolol and bevacizumab with betamethasone to prevent corneal neovascularization (CNV) in rabbits. This study was performed on 28 male rabbits. CNV was induced by three 7-0 silk sutures 2 mm long and 1 mm distal to the limbus. Animals were randomly divided into 4 groups of propranolol + betamethasone, timolol + betamethasone and bevacizumab + betamethasone and betamethasone alone. Eye drops were started from the first day of study. On 7th, 14th, 21st, 28th, 35th and 42nd days, vascular progression, time of neovascularization and vascular area were evaluated and compared with the control group (betamethasone alone). There was a significant reduction in the area of neovascularization in the timolol and bevacizumab groups compared to the control group (P-value = 0.05, P=0.047, respectively). Also, regarding vascular progression, there was a significant decrease in the timolol and bevacizumab groups (P-value = 0.014, P=0.002, respectively). Regarding delayed onset of neovascularization, there was a significant difference in the timolol and bevacizumab group in rabbits (P-value = 0.04, P=0.00, respectively). In conclusion, the use of timolol and bevacizumab drops besides betamethasone can delay neovascularization and decrease the length of corneal vascularization in rabbits.

The aim of this study was using a temporary collagen punctal plug as a pre-test before decision of permanent punctal closure or long-term plug use for patients with dry eye disease (DED) and primary open-angle glaucoma (POAG). This case-control study was conducted at a single office in Honolulu, Hawaii from January 2017 to August 2018. In the case group, a temporary collagen plug was used in 33 eyes of 33 patients with DED and POAG who were receiving glaucoma medications with good control. On the other hand in the control group, 33 eyes of 33 patients with DED and POAG who were receiving glaucoma medications with good control were included, but punctal plug was not used. In the case group, one of the lower lid puncta was selected for the study and a canalicular rod shape plug was inserted as a therapeutic trial to predict the efficacy of long-term punctal plug placement or punctal closure. The mean changes of intraocular pressure (IOP) and improvement in symptoms/signs of DED were compared between the two study groups. Results revealed a statistically significant IOP reduction in the case group compared to the control group. Furthermore, DED improved significantly more in the case group compared to the control group (P< 0.001). We concluded that temporary punctal plug in patients with DED and POAG can significantly improve DED and lower IOP. Therefore, we could consider permanent punctal closure or long-term plug for patients with DED and POAG who responded well to temporary punctal plug without epiphora or other complications.

We aimed to determine true and false positives of glaucoma screening, relying solely on photos of the retina, taken with a smartphone. We performed a descriptive and analytical study on patients with type 2 diabetes at the National Obesity Centre, Yaounde, Cameroon. Participating patients had retinal photography sessions using an iPhone 5s (iOS 10.3.3; Apple, Cupertino, CA) coupled to the Make in India Retinal Camera (MIIRetCam; MIIRetCam Inc., Coimbatore, TN, India). Obtained pictures of the retina were stored and transferred via the internet to an ophthalmologist to assess glaucoma. Selected patients were then invited to undergo a conventional ophthalmological examination to confirm the diagnosis. A total of 395 patients were screened, 39 (including 20 women) were diagnosed with suspicion of glaucoma based on retinal photos, a prevalence rate of 9.87%. The following signs were found; C/D equal or more than 0.5 in 64.1% (25/39), asymmetric C/D >0.2 in 35.9% (14/39), papillary haemorrhage in 10.2% (4/39) and retinal nerve fibre deficiency in 2.5% (1/39). Only 14 of 39 patients with suspicion of glaucoma were examined, giving a lost-to-follow-up rate of 64.1%. Chronic open-angle glaucoma was confirmed in 8 patients (true positives) and absent in 6 patients (false positives). The prevalence of smartphone-detected glaucoma and lost-to-follow-up rates were high. So we need to improve this type of screening, with additional tests like transpalpebral applanation tonometer and the smartphone Frequency Doubling Technique visual field combined with better education of patients to increase their adherence to follow-up.

Ocular accommodation is not just a mechanism for altering curvature of the crystalline lens of the eye, it also enables aqueous humor outflow through the trabecular meshwork, influencing intraocular pressure (IOP). Long term stress on the ciliary muscle from sustained near focusing may initiate myopic eye growth in children and primary open angle glaucoma in presbyopic adults. Multi-factorial studies of ocular accommodation that include measures of IOP, ciliary muscle morphology, anterior chamber depth, and assessment of nutritional intake and metabolic markers may elucidate etiology and novel strategies for management of both myopia and chronic glaucoma. Anatomy of the ciliary fibers from anterior insertion in the fluid drainage pathway to their posterior consanguinity with the vascular choroid, alters ocular parameters such as micro-fluctuations of accommodation and pulsatile ocular blood flow that are driven by cardiac contractions conveyed by carotid arteries. Stretching of the choroid has consequences for thinning of the peripheral retina, sclera and lamina cribrosa with potential to induce retinal tears and optic nerve cupping. It is hoped that the present synthesis of relevant literature and evidence based speculations, may stimulate additional research conducted clinically oriented scientists, supported by their host institutions. Early metabolic interventions may lead to prevention or reduced severity of myopia and glaucoma. It is hoped that improved quality of life for patients and informed consumers, and reduced disability from visual impairment and blindness may result.