The Antiangiogenic Properties of Adipose-Derived Mesenchymal Stem/Stromal Cells in Corneal Neovascularization in a Rabbit Model

Demetrios Pirounides, Anastasia Komnenou, Nikolaos Papaioannou, Eleni Gounari, Ioanna Stylianaki, Alexandros Alexandridis, Angeliki Chranioti, Evangelia Kofidou, Georgios Koliakos, Vasileios Karampatakis

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 74-84

The purpose was to study the anti-angiogenic effect of adipose-derived mesenchymal stem/stromal cells (ADMSCs) on experimentally induced corneal injuries. Corneal neovascularization (NV) was induced by incising and subsequently suturing the corneal surface in 32 New Zealand rabbits. Following suturing, the rabbits were randomly allocated into 2 groups, and received either phosphate-buffered saline (PBS) (control) or ADMSCs, both administered via three different routes. Digital images of the cornea were obtained two weeks post-incision to measure the area of neovascularized cornea. Tumor necrosis factor (TNF) was immunohistochemically assessed in the both groups. The corneal tissue was evaluated for vascular endothelial growth factor (VEGF). The extent of corneal NV in all eyes was assessed photographically by an independent observer. Fourteen days after the incisions, the degree of corneal NV was substantially decreased in the ADMSC-treated group (1.87 ± 0.9 mm2, 1.4 % ± 0.67 % of corneal surface) compared to the control and PBS-treated group (4.66 ± 1.74 mm2, 3.51 % ± 1.31 %, p < 0.001). ADMSCs significantly decreased injury-induced corneal NV in New Zealand rabbits two weeks post-treatment. This strategy has potential for use in the control of corneal NV in vivo.


Bilateral Double-headed Recurrent Pterygium: A Case Presentation and Literature Review

Bengi Ece Kurtul, Ahmet Kakac, Abdulkerim Karaaslan

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 85-90

Pterygium is a frequent corneal disease characterized by growing of fibrovascular tissue from the bulbar conjunctiva onto the cornea. Although the causes of pterygium are not obvious, sun exposure is closely correlated with its development. Pterygium, especially double-headed pterygium is mostly seen in warm climate and in individuals who work outdoors.A minority of pterygium is double-headed (both temporal and nasal origins). Bilateral recurrent double-headed pterygium is a very rare condition. Here, we reported a 35-year-old male patient with bilateral recurrent double-headed pterygium. A brief review about the recent literature concerning the etiology, associated risk factors, operation types and management of patients with recurrent pterygium was also discussed. The patient was a field worker, smoker and had a family history of pterygium. There was no ocular surgery history except pterygium surgery 15 years ago in both eyes. A successful pterygium excision was performed under local anesthesia with the vertical split conjunctival autograft transplantation (CAT) in both temporal and nasal parts of the right eye (randomly) for cosmetic disfigurement and avoidance of recurrence. The pathological report was consistent with pterygium. At postoperative first week, first and 1.5th month visits, conjunctival autografts were in place and stable. No complications such as infection, corneal thinning or graft dislocation were seen. The patient was satisfied with his right eye and demanded the same surgery for his left eye. We suggest vertical split simultaneous CAT as a safe and useful surgical method for the treatment of recurrent double-headed pterygium; however, longer follow-up is required to confirm the outcome.

A Review of Last Decade Developments on Epiretinal Membrane Pathogenesis

Eleni Tsotridou, Eleftherios Loukovitis, Konstantinos Zapsalis, Iro Pentara, Solon Asteriadis, Paris Tranos, Zachos Zachariadis, George Anogeianakis

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 91-110

Epiretinal membrane (ERM) is a pathologic tissue that develops at the vitreoretinal interface. ERM is responsible for pathological changes of vision with varying degrees of clinical significance. It is either idiopathic or secondary to a wide variety of diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). A great variation in the prevalence of idiopathic ERM among different ethnic groups proposed that genetic and lifestyle factors may play a role in ERM occurrence. Histopathological studies demonstrate that various cell types including retinal pigment epithelium (RPE) cells, fibrocytes, fibrous astrocytes, myofibroblast-like cells, glial cells, endothelial cells (ECs) and macrophages, as well as trophic and transcription factors, including transforming growth factor (TGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) etc., are directly or indirectly involved in the pathogenesis of  idiopathic or secondary ERMs. These processes are driven (on the last count) by more than 50 genes, such as Tumor Necrosis Factor (TNF), CCL2 ((chemokine (C-C motif) ligand 2)), MALAT1, transforming growth factor (TGF)-β1, TGF-β2, Interleukin-6 (IL-6), IL-10, VEGF and glial fibrillary acidic protein (GFAP), some of which have been studied more intensely than others. The present paper tried to summarize, highlight and cross-correlate the major findings made in the last decade on the function of these genes and their association with different types of cells, genes and gene expression products in the ERM formation.

Oculocardiac Reflex During Intravitreal Injection

Miguel Paciuc-Beja, Daniela Meizner-Grezemkovsky, Mario Paciuc, Idaira Sanchez-Santos, Anabeli Ruiz-Roman, Ashlee Fack, Andres Lisker-Cervantes, Gerardo Mendieta, Virgilio Morales-Canton, Hugo Quiroz-Mercado

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 111-117

Oculocardiac reflex (OCR) has been described to occur with mechanical manipulation of the eye, eyelids or orbit. There are no reports in the literature of OCR during intravitreal injection (IVI). This may be due to the fact that heart rate is not monitored during the procedure. We aimed to evaluate OCR during IVI. A total of 532 patients were enrolled in the study in Asociacion para Evitar la Ceguera en Mexico. Mexico City, Mexico. IVI was performed on one eye in every patient with diabetic retinopathy (DR), age related macular degeneration (AMD) or choroidal neovascularization (CNV) secondary to pathological myopia. Heart rate was monitored with a pulse oximeter before, during and after injection. OCR was defined as a 20% decrease or more of basal heart rate. The population enrolled included 270 females and 262 males with mean age of 63.8 years. A decrease in heart rate of 20% or more occurred in 18 patients during IVI (3.3%; 95% confidence interval 1.85% and 4.92%). OCR was asymptomatic in these patients. OCR occurred in 3.3% of our patients during IVI. Hence, OCR must be considered when performing IVI.

Inflammatory Choroidal Neovascular Membranes in Patients With Noninfectious Uveitis: The Place Of Intravitreal Anti-VEGF Therapy

Omer Karti, Sefik Can İpek, Yesim Ates, Ali Osman Saatci

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 118-126

Inflammatory choroidal neovascularization (iCNV) is an infrequent but an important cause of visual morbidity in patients with non-infectious uveitis and mostly occurs in intermediate or posterior uveitis. Punctate inner choroiditis, Vogt-Koyanagi-Harada disease and multifocal choroiditis are among the leading causes of uveitis entities resulting in iCNVs. The diagnosis and management of iCNVs still remain a challenge. Use of multimodal imaging techniques such as fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT) and OCT-angiography may be necessary for the diagnosis of iCNVs. The treatment algorithm is not straightforward for iCNV. While control of the active inflammation with steroids and/or immunosuppressive agents is a key to success, various adjunctive treatment modalities such as thermal laser photocoagulation, photodynamic therapy and surgical membrane removal were also coadministered previously. Nowadays, vascular endothelial growth factor (VEGF) inhibitors has become the most commonly administered adjunctive treatment option as they provide better anatomical and functional outcome and the recurrence rate of CNV is relatively low. We hereby reviewed important clinical studies and case series on anti-VEGF administration in iCNVs and briefly overviewed their results.

Peripheral Cornea Crosslinking Before Deep Anterior Lamellar Keratoplasty

Mohammed Ziaei, Akilesh Gokul, Hans Vellara, Dipika Patel, Charles NJ McGhee

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 127-134

Since Cornea crosslinking (CXL) has been proven to halt progression and biomechanically stabilize keratoconus, we hypothesized that CXL of the corneal periphery 3 months prior to corneal transplantation can reduce the incidence of recurrent ectasia by strengthening the peripheral corneal tissue and causing apoptosis of diseased peripheral host keratocytes. Thus, the aim of this case-repot was to propose a novel peripheral CXL technique prior to keratoplasty and evaluate its safety. A 22-year-old woman was admitted with advanced right keratoconus and corrected distance visual acuities of 20/30 in the right eye and 20/200 in the left eye with a manifest refraction of -3.00 -8.00 × 36 and -17.00 -11.50 × 90, respectively. The proposed treatment involved crosslinking of peripheral corneal tissue (6.5-9.5mm), sparing the central cornea and limbus, three months prior to corneal transplantation as a means of biomechanically strengthening the peripheral cornea tissue. We performed peripheral CXL technique in a patient with keratoconus undergoing deep anterior lamellar keratoplasty (DALK). This procedure was feasible and safe with repopulation of the peripheral cornea with keratocytes and no significant endothelial cell loss. This method might reduce or eliminate the need for repeat corneal transplantation in patients with recurrent ectasia. Further studies are needed to confirm the results.

The Effect of Age on Corneal Topographic Indices, Keratometry and Visual Acuity After Combined Intrastromal Corneal Ring Segment (ICRS) Implantation and Corneal Crosslinking

Sylvain El-Khoury, Youssef Abdelmassih, Mazen Amro, Ali Dirani, Carol Cherfan, Elias Jarade

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 135-142

We aimed to assess age-related changes in corneal topographic indices, keratometry and visual acuity after sequential intracorneal ring segment implantation (ICRS) and crosslinking (CXL). This was a retrospective matched case-control series including 26 eyes of patients ≤18 years as the cases and 26 eyes of adult patients as control. All eyes received ICRS+CXL for progressive keratoconus. Eyes were matched regarding the keratoconus parameters and the treatment (type, number and thickness of ICRS). Data was analyzed for refractive and topographic values [uncorrected and corrected distance visual acuity (UDVA; CDVA) sphere; cylinder; spherical equivalent; maximum keratometry (Kmax); flat keratometry (Kflat); steep keratometry (Ksteep); all 7 pentacam topographic indices] preoperatively and one year postoperatively. Preoperatively, there was no significant difference for any refractive, clinical or topographic parameters between the groups except for vertical asymmetry. After one year, children had a significantly higher improvement in Ksteep (3.05D) than adults (2.10D; P=0.036) and a trend to significance for Kflat (2.7D compared to 1.78D, respectively; P=0.081). UDVA improved by 4.3 ETDRS lines in children compared to 3.3 ETDRS lines in adults and CDVA improved by 1.7 ETDRS lines in children compared to 1.2 ETDRS lines in adults, but with no statistical significance. The effects on keratometry indicated that corneal response after ICRS and CXL for keratoconus is more pronounced in young patients than adults. This assumption is also supported by functional improvement and by the fact that a few eyes (5) of some very young patients (<13years) showed highly remarkable improvements after surgery (higher than any adult eye).

Is Palpation Sufficient for Estimation of IOP Immediately Following Cataract Surgery?

Andrew J Polk, Van Nguyen, John Jarstad

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 143-148

The aim of this study was to evaluate the accuracy of standard palpation techniques and Barraquer tonometry relative to Tono-Pen for measurement of postoperative intraocular pressure (IOP) immediately following routine micro-incision cataract surgery (MICS). We conducted a prospective comparative analysis of postoperative IOP immediately after MICS in a single academic outpatient surgery center. A random block of 166 eyes that underwent MICS at our institution included in our study. Exclusion criteria consisted of any complications including posterior capsule rupture. IOP was measured immediately postoperatively, first with palpation or a Barraquer tonometer, then with a Tono-Pen handheld applanation tonometer. Measurements obtained by each method were compared. The mean difference between IOP measurements obtained by palpation and Tono-Pen was 10 mmHg, 95% confidence interval (CI; 8, 12); whereas the mean difference between IOP measurements obtained by Barraquer tonometer and Tono-Pen was 2 mmHg, 95% CI (1, 3). IOP measurements acquired via palpation differed from their corresponding Tono-Pen measurements by > 5 mmHg in 48.0% of cases compared to only 5.9% of measurements acquired using a Barraquer tonometer. Spearman correlation coefficient for measurements obtained by standard palpation and Tono-Pen was r = 0.397 (p < 0.01) compared to r = 0.774 (p < 0.01) for those obtained by Barraquer tonometer and Tono-Pen. In conclusion, palpation is not an accurate method for estimating IOP immediately after cataract surgery compared to Tono-Pen. Appropriate measurement and adjustment of IOP after the operation may decrease complications such as cystoid macular edema.In settings where a Tono-Pen is not readily available, Barraquer tonometry may serve as a reasonable and cost-effective alternative.

COVID-19: Preliminary Clinical Guidelines for Ophthalmology Practices

Reza Gharebaghi, Jordan Desuatels, Majid Moshirfar, Maryam Parvizi, Seyed-Hashem Daryabari, Fatemeh Heidary

Medical Hypothesis, Discovery & Innovation in Ophthalmology, Vol. 9 No. 2 (2020), 4 March 2020 , Page 149-158

The zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant human coronavirus disease (COVID-19) recently appeared as a global health threat that can cause severe respiratory infection and terminal respiratory distress. By the first week of April, more than 1.3 million people had been globally infected and more than 70,000 had lost their lives to this contagious virus. Clinical manifestations occur shortly after exposure, or a few days later. There is controversy regarding the transmission of the virus through the tear and conjunctiva; however, there are reports that the ocular surface might be a potential target for COVID-19. The ease of transmission of this virus at close proximity presents a risk to eyecare workers. Several recommendations have been issued by local and national organizations to address the issue of safe ophthalmic practice during the ongoing COVID-19 pandemic. These guidelines have numerous similarities; however, subtle differences exist. The purpose of this paper was to discuss measures, with a specific focus on standard precautions, to prevent further dissemination of COVID-19 at Eye Clinics. We have proposed procedures to triage suspected cases of COVID-19, considering emergency conditions.

Photo Courtesy of Majid Moshirfar, MD FACS.