Journal of Ophthalmic and Vision Research
Volume:15 Issue: 4, Oct-Dec 2020

To evaluate the penetration of carbon nanotubes (CNTs) throughout retinoblastoma in a transgenic mice model.

CNTs functionalized with fluorescein isothiocyanate and targeting ligands biotin (CTN-FITC-Bio, 0.5mg/ml), or folic acid (CNT-FITC-FA, 0.5mg/ml) were injected into the vitreous of one eye of LHBETATAG transgenic mice. Other eye did not receive any injection and was used as control. Three mice were sacrificed at days 1, 2, and 3. Eyes were enucleated and stained with 4,6-diamidino-2-phenylindole. The sections were imaged by fluorescent microscope. The images were transformed into grey-scale in MATLAB for intensity analysis. Background intensity was normalized by marking squares outside the eyeball and using the mean intensity of these squares. Fluorescent intensity (FI) for each image was measured by calculating the intensity of a same-sized square within retinoblastoma.

Nine eyes of nine mice were included in each CNT-FITC-Bio and CNT-FITC-FA groups. The mean FI in CNT-FITCBio was 52.08 ± 6.33, 53.62 ± 9.00, and 65.54 ± 5.14 in days 1, 2, and 3, respectively. The mean FI in CNT-FITC-FA was 50.28 ± 7.37, 59.21 ± 6.43, and 58.38 ± 2.32 on days 1, 2, and 3, respectively. FI was significantly higher in eyes injected with CNT-FITC-Bio and CNT-FITC-FA compared to the control eyes (P = 0.02). There was no difference in FI between eyes with CNT-FITC-Bio and CNT-FITC-FA, and FI remained stable on days 1–3 in CNT-FITC-Bio, CNT-FITC-FA, and control eyes (P > 0.05).

We observed higher FI in eyes with CNT-FITC-Bio and CNT-FITC-FA compared to control eyes, showing penetration of CNTs throughout retinoblastoma. CNTs can be a carrier candidate for imaging or therapeutic purposes in retinoblastoma.

To report the efficacy of topical interferon alpha 2b in the treatment of refractory diabetic macular edema.

In this retrospective interventional case series, five eyes of three individuals with diabetic macular edema resistant to multiple intravitreal injections of anti-vascular endothelial growth factor drugs and macular photocoagulation were included.

All studied eyes had undergone multiple intravitreal injections including bevacizumab, combination of bevacizumab and triamcinolone and aflibercept, and macular laser photocoagulation before being included in this study. Two intravitreal ranibizumab injections had also been performed in both eyes of one patient. Two eyes had undergone pars plana vitrectomy, one for diabetic macular edema and the other for rhegmatogenous retinal detachment. After a discussion regarding the experimental topical interferon alpha 2b treatment, all patients agreed to start interferon alpha 2b drops four times a day. One month after the treatment, optical coherence tomography demonstrated a significant improvement in macular structure and thickness which was stable or improved at the three-month follow-up visit. Visual acuity in all eyes was stable or improved throughout the three-month follow-up period. Conjunctival injection and follicular conjunctivitis were the side effects of topical interferon alpha 2b and were treated with lubrication and steroids.

This case series demonstrated the potential efficacy of interferon alpha 2b in the treatment of refractory diabetic macular edema. It might be an option in patients with contraindications for intravitreal injections.

To determine the efficacy and safety of infliximab therapy in patients with HLA B-27-associated ocular inflammation resistant or intolerant to conventional immunomodulatory therapy.

This was a retrospective observational case series. All cases were uveitic patients with positive HLA-B27, confirmed through HLA testing, resistant or intolerant to conventional immunomodulatory therapy. The primary outcome of the study was to identify the efficacy of infliximab determined by the control of inflammation, duration of remission, and the ability to reduce conventional immunomodulatory therapy. The secondary outcome was an improvement of two or more lines of best-corrected visual acuity (BCVA) on the Snellen visual acuity chart.

Twenty-four patients (38 eyes) were included in the study. All patients were followed for 24 months. Twenty-one (87.5%) patients completed 24 months of follow-up. Sixteen (66.7%) patients had active uveitis at the beginning of therapy. One patient out of these active patients had active inflammation at the end of follow-up period. Thirteen (87.5%) out of sixteen active patients were in steroid-free remission. The mean duration of treatment to induce remission was 16.5 months (range 6–24 months). Corticosteroid was stopped in 19 (90.5%) patients by the end of the study. At the end of the study, in patients who achieved remission, 14 (58.3%) patients were in remission on infliximab therapy and 6 (25%) patients were in remission off infliximab therapy. Of the 38 eyes, 8 (21.05%) showed improvement in BCVA (three eyes had successful cataract extraction with intraocular lens implantation during infliximab therapy with no subsequent inflammation), while 26 eyes (68.4%) had stable BCVA over the 24-month study period. The side effects included allergic reaction, fatigue, cellulitis, headache, restlessness, elevation of liver enzymes, and anemia. Two patients (n = 24, 8.3%) experienced severe adverse effects and the treatment was stopped prematurely in these two patients.

Infliximab might induce and maintain the steroid-free remission in HLAB27- associated ocular inflammation in patients resistant or intolerant to conventional immunomodulatory therapy.

7-ketocholesterol (7kCh), a natural byproduct of oxidation in lipoprotein deposits is implicated in the pathogenesis of diabetic retinopathy and age-related macular degeneration (AMD). This study was performed to investigate whether several clinical drugs can inhibit 7kCh-induced caspase activation and mitigate its apoptotic effects on retinal cells in vitro.

Two populations of retinal cells, human retinal pigment epithelial cells (ARPE-19) and rat neuroretinal cells (R28) were exposed to 7kCh in the presence of the following inhibitors: Z-VAD-FMK (pan-caspase inhibitor), simvastatin, memantine, epicatechin, and Z-IETD-FMK (caspase-8 inhibitor) or Z-ATAD-FMK (caspase-12 inhibitor). Caspase-3/7, -8, and -12 activity levels were measured by fluorochrome caspase assays to quantify cell death. IncuCyte live-cell microscopic images were obtained to quantify cell counts.

Exposure to 7kCh for 24 hours significantly increased caspase activities for both ARPE-19 and R28 cells (P < 0.05). In ARPE cells, pretreatment with various drugs had significantly lower caspase-3/7, -8, and -12 activities, reported in % change in mean signal intensity (msi): Z-VAD-FMK (48% decrease, P < 0.01), memantine (decreased 47.8% at 1 μM, P = 0.0039 and 81.9% at 1 mM, P < 0.001), simvastatin (decreased 85.3% at 0.01 μM, P < 0.001 and 84.8% at 0.05 μM , P < 0.001) or epicatechin (83.6% decrease, P < 0.05), Z-IETD-FMK (68.1% decrease, P < 0.01), and Z-ATAD-FMK (47.7% decrease, P = 0.0017). In contrast, R28 cells exposed to 7kCh continued to have elevated caspase- 3/7, -8, and -12 activities (between 25.7% decrease and 17.5% increase in msi, P > 0.05) regardless of the pretreatment.

Several current drugs protect ARPE-19 cells but not R28 cells from 7kChinduced apoptosis, suggesting that a multiple-drug approach is needed to protect both cells types in various retinal diseases.

To evaluate the ectasia risk score system in cancelled laser in situ keratomileusis (LASIK) candidates at an academic hospital.

LASIK candidates who had been cancelled by a surgeon considering the patient age, preoperative central corneal thickness, residual stromal bed thickness, or preoperative manifest refraction spherical equivalent were retrospectively reviewed, and their Randleman ectasia risk score system score was calculated.

The mean ectasia score of 194 eyes (97 patients) was 4.5 ± 2.67; 40 (20.6%), 46 (23.7%), and 108 (55.7%) eyes were classified as low-, moderate-, and high-risk eyes, respectively. The topography was abnormal in 69% of the patients. The mean manifest refraction spherical equivalent, central corneal thickness, and estimated residual stromal bed thickness were 4 (+0.50 to –15.50) diopters, 520 (439 to 608) μm, and 312.38 (61.5 to 424.12) μm, respectively. The main cause of cancellation in low- and moderate-risk patients (86 eyes) was the presence of unstable refractive error in the past year.

Although promising, some other criteria, such as stable refraction, should be added to this scoring system to achieve greater practicality since a main cause of cancelling LASIK candidates in this study was the presence of unstable refraction.

To evaluate the safety and efficacy of femtosecond laser-assisted MyoRing implantation with concurrent corneal collagen crosslinking (CXL) compared to MyoRing alone for the treatment of progressive keratoconus.

A total of 60 patients were enrolled in this randomized controlled trial. The patients were randomly allocated into two groups. In the first group, MyoRing was implanted, while in the second, it was inserted in the corneal stroma using the same technique, along with simultaneous CXL. Visual, refractive, topographic, and abberometric outcomes were measured preoperatively and at every postoperative visit.

Data of 47 patients were available at the end of the study; 28 in the MyoRing group and 19 in the MyoRing + CXL group. The mean uncorrected distance visual acuity (UDVA) improved from 0.79 ± 0.39 logMAR to 0.52 ± 0.31 logMAR (P < 0.05) in the MyoRing + CXL group and from 0.65 ± 0.38 logMAR to 0.62 ± 0.23 logMAR (P = 0.70) in the MyoRing group. CDVA changed from 0.33 ± 0.19 logMAR to 0.25 ± 0.16 logMAR (P = 0.10) in the MyoRing + CXL group and 0.32 ± 0.22 logMAR to 0.33 ± 0.17 logMAR (P > 0.50) in the MyoRing group. The mean keratometry (Km) decreased from 47.5 ± 2.7 D to 43.8 ± 3.2 D (P < 0.001) in the MyoRing group and 49.3 ± 3.4 D to 45.1 ± 3.0 D (P < 0.001) in the MyoRing + CXL group. Besides, horizontal coma was significantly lower in the MyoRing + CXL group (P = 0.022).

MyoRing insertion combined with CXL is a safe and effective method for the treatment of keratoconus. The visual and topographic outcomes were comparable to that for MyoRing insertion after 10 months; however, horizontal coma was significantly lower in the MyoRing + CXL group.

To reveal the phenotypic differences between human ocular surface stromal cells (hOSSCs) cultured from the corneal, limbal, and scleral compartments.

A comparative analysis of cultured hOSSCs derived from four unrelated donors was conducted by multichromatic flow cytometry for six distinct CD antigens, including the CD73, CD90, CD105, CD166, CD146, and CD34.

The hOSSCs, as well as the reference cells, displayed phenotypical profiles that were similar in high expression of the hallmark mesenchymal stem cell markers CD73, CD90, and CD105, and also the cancer stem cell marker CD166. Notably, there was considerable variation regarding the expression of CD34, where the highest levels were found in the corneal and scleral compartments. The multi-differentiation potential marker CD146 was also expressed highly variably, ranging from 9% to 89%, but the limbal stromal and endometrial mesenchymal stem cells significantly surpassed their counterparts within the ocular and reference groups, respectively. The use of six markers enabled investigation of 64 possible variants, however, just four variants accounted for almost 90% of all hOSSCs, with the co-expression of CD73, CD90, CD105, and CD166 and a combination of CD146 and CD34. The limbal compartment appeared unique in that it displayed greatest immunophenotype diversity and harbored the highest proportion of the CD146+CD34- pericyte-like forms, but, interestingly, the pericyte-like cells were also found in the avascular cornea.

Our findings confirm that the hOSSCs exhibit an immunophenotype consistent with that of MSCs, further highlight the phenotypical heterogeneity in stroma from distinct ocular surface compartments, and finally underscore the uniqueness of the limbal region.

Glaucoma causes irreversible visual field defects. This study aims to evaluate the effect of a reversed Galilean telescope on the visual field of patients with open-angle glaucoma.

Fifty-two glaucoma patients with a restricted visual field were recruited for this study. Central 30° visual field measurements were performed using a Humphrey visual field analyzer before and after applying the reversed Galilean telescope. To be more cosmetically acceptable, a combination of contact lens–spectacle was used as the reversed Galilean telescope.

Our data analysis showed that the reversed Galilean telescope had a significant effect on all measured perimetric indices. Visual field index (VFI) improved from a basic value of 44.38 ± 26.96 to 49.30 ± 29.83 percent by using the reversed telescope (P < 0.001). Moreover, the mean deviation (MD) was significantly improved from the initial value of –19.91 ± 7.19 dB to a value of –18.69 ± 7.73 dB (P < 0.001). However, our results showed a significant reduction in the pattern standard deviation (PSD) comparing before (9.83 ± 2.82) and after (8.51 ± 3.30) values using the reversed Galilean telescope (P < 0.001).

The contact lens–spectacle combination reversed Galilean telescope significantly improved the central 30° visual field of glaucoma patients with the restricted visual field.

To assess the efficacy and survival rate of the Trabectome-mediated ab interno trabeculectomy combined with non-fenestrated Baerveldt glaucoma implant compared with the Baerveldt glaucoma implant alone.

In this retrospective comparative case series, 175 eyes undergoing primary glaucoma surgery (Baerveldt–Trabectome [BT] group: 60 eyes and Baerveldt [B] group: 115 eyes) were included. Participants were identified using the procedural terminology codes. Groups were then matched by Coarsened Exact Matching that resulted in the inclusion of 51 eyes in each group. The primary outcome measure was surgical success defined as 5 mmHg < intraocular pressure (IOP) ≤ 21 mmHg, and IOP reduction ≥ 20% from baseline, and no need to reoperation for glaucoma. Secondary outcome measures were IOP, number of glaucoma medications, and best-corrected visual acuity (BCVA).

The cumulative probability of success at one year was 61% in the BT group and 50% in the B group. IOP decreased from 23.5 ± 2.4 mmHg at baseline to 14.1 ± 2.7 mmHg at the final follow-up in the BT group (P = 0.001). The corresponding values for the B group were 23.2 ± 2.0 mmHg and 13.9 ± 1.6 mmHg, respectively (P = 0.001). There was no significant difference between the groups in terms of IOP at the final follow-up (P = 0.56). The number of medications at baseline was 2.3 ± 0.3 in both groups. However, the BT group needed fewer drops at all postoperative time intervals and used 1.1 ± 0.3 versus 2.0 ± 0.4 eye drops (group B) at the final follow-up visit (P = 0.004). Eyes in B with phacoemulsification had a significantly higher IOP on day 1 compared to B (23.2 ± 14.3 versus 17.9 ± 11.4, P = 0.041). During the oneyear follow-up, 7 (13.7%) patients in BT group and 18 (35.2%) in B group experienced hypotony (P = 0.04). No dangerous hypotony or hypertension occurred in BT group. The mean BCVA at baseline was 0.64 ± 0.85 logMAR and changed to 0.55 ± 0.75 logMAR in BT and B groups, respectively (P = 0.663). The corresponding numbers for the final follow-up visit was 0.72 ± 1.07 and 0.63 ± 0.97 logMAR, respectively (P = 0.668).

We observed similar rates of success and IOP reduction using BT and B techniques. BT group needed fewer glaucoma medications. Tube fenestration was unnecessary in BT group resulting in less postoperative ocular hypotony and hypertension. The results of our study indicate that additional trabectome procedure makes Baerveldt glaucoma implant safer, easier to handle, and more predictable in the most vulnerable patients with advanced glaucoma.

To compare the area of the foveal avascular zone (FAZ) in the superficial and deep retinal layers using two different spectral-domain optical coherence tomography angiography (OCTA) devices.

A cross-sectional comparative study was conducted to obtain macular OCTA images from healthy subjects using Optovue RTVue XR Avanti (Optovue, Inc, Fremont, CA) and Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany). Two independent trained graders measured the FAZ area using automated slab segmentation. The FAZ area in the superficial and deep retinal layers were compared.

Twenty-three eyes of 23 subjects were included. The graders agreement was excellent (>0.86) for all measurements. The mean FAZ area was significantly larger at the superficial retinal layer as compared to the deep retinal layer on both devices (0.31 ± 0.08 mm2 vs 0.26 ± 0.08 mm2 in Optovue and 0.55 ± 0.16 mm2 vs 0.36 ± 0.13 mm2 in Spectralis, both P < 0.001). The mean FAZ area was significantly greater in the superficial and deep retinal layers using Spectralis as compared to Optovue measurements (P < 0.001 for both comparisons).

In contrast to previous reports, the FAZ area was larger in the superficial retina as compared to deep retinal layers using updated software versions. Measurements from different devices cannot be used interchangeably.

Different patterns of diabetic macular edema (DME) suggest different pathogenesis and drug response. We evaluated the outcomes after intravitreal dexamethasone (DEX) implant for DME with or without serous retinal detachment (SRD).

In this retrospective study, 22 naïve patients (23 eyes) with DME who underwent a single DEX implant were evaluated. Based on the optical coherence tomographic pattern of DME, 12 eyes had a cystoid macular edema pattern (Group 1) and 11 eyes had an SRD pattern (Group 2). The best-corrected visual acuity (BCVA), central retinal thickness (СRТ), central retinal volume (CRV), SRD height (SRDh), and intraocular pressure (IOP) were recorded before and at two and four months after the treatment.

There were no significant differences between the groups regarding demographic, clinical data and outcomes at baseline. In Group 1, the CRT and CRV significantly decreased at two months (P = 0.002 and P = 0.01, respectively), while the BCVA significantly improved at four months (P = 0.03). In Group 2, the CRT and CRV significantly improved (P < 0.01 and P ≤ 0.01, respectively) during the follow-up period. At four months, both groups showed a recurrence of DME, Group 1 in particular (two-month CRT reduction, –149 ± 127 μm vs four-month CRT reduction, –72 ± 174 μm; P = 0.04). The mean reduction in CRV was significantly different at four months (Group 1, –0.49 ± 1.7 mm3 vs Group 2, –1.3 ± 1.3 mm3; P = 0.04). In Group 2, the SRDh significantly decreased at two (P = 0.01) and four months (P = 0.01). Four cases with elevated IOP were managed.

DEX implants were found to be effective in different patterns of DME. The SRD pattern may predict a longer-lasting morphologic efficacy.

Glaucoma management has changed dramatically over the last decades, through clinical advances and technological revolutions. This review discusses the latest innovations and challenges faced in the field around three major axes: minimally-invasive glaucoma surgery (MIGS), implantable sensors and injectable therapeutics. Indeed, the vast number of recently developed MIGS techniques has not only provided clinicians with a wide range of therapeutic options, but they have also enabled them to adjust their therapies more finely which may have contributed a more patient-centric decision-making process. Yet, despite considerable advances in the field, the wide heterogeneity in clinical trial designs blurs the surgical outcomes, specificities and indications. Thus, more high-quality data are required to make the choice of a specific MIGS procedure more than an educated guess. Beyond the scope of MIGS, the potential of IOP telemetry for self-assessment of IOP-control through implantable sensors is developing into a real option for clinicians and an empowering opportunity for patients. Indeed, providing patients with direct feedback enables them to take control and have a clearer representation of their care, in turn leading to a better control of the disease. However, there are potential issues with self-monitoring of IOP, such as increased anxiety levels induced by measured IOP fluctuations and peaks, leading to patients self-treating during IOP spikes and additional office visits. Furthermore, the advent of implantable therapeutics may soon provide yet another step towards personalized glaucoma treatment, by offering not only an efficient alternative to current treatments, but also a therapeutic option that may better adapt to patients’ lifestyle. After several decades of relative stagnation through the last century, glaucoma has now entered what many view as a golden age for the specialty. Like every revolution, this one brings its fair share of uncertainty, clinical questioning and uneasy periods of adaptation to ever-changing expectations. Yet, while it is impossible to guess what the landscape of glaucoma surgery will be like in ten or fifteen years, data suggest a bright outlook both for patients and clinicians.

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.

To present a case of central serous chorioretinopathy (CSC) in association with regressed familial retinoblastoma.

A 23-year-old man with regressed unilateral familial retinoblastoma in his left eye presented with decreased vision of the left eye since two months ago. The patient had undergone chemotherapy and cryotherapy for the treatment of retinoblastoma 20 years ago. In the left eye, funduscopy disclosed regressed mass of retinoblastoma, inferonasal to the optic disc, and focal subfoveal neurosensory detachment. Optical coherence tomography (OCT) and fluorescein angiography revealed CSC. As there was no sign of recurrence of retinoblastoma and retinal findings did not show late-onset chemotherapy-related retinopathy, the patient was diagnosed with CSC and followed up. After two months, visual acuity of the left eye improved, and repeated macular OCT revealed absorption of the subretinal fluid.

Subretinal fluid accumulation in a patient with regressed retinoblastoma is not always a sign of tumor recurrence or a treatment-related retinopathy. 

To describe the clinical and histopathological findings of a case of intraocular metastasis due to colorectal adenocarcinoma and to carry out a literature review.

A 64-year-old man with a history of tumor resection due to infiltrating colorectal adenocarcinoma three years previously sought ophthalmological care because of severe ocular pain without response to medical treatment and progressive vision loss in the left eye. On ultrasonographic examination, there was a heterogeneous intraocular choroidal tumor, which occupied approximately 40% of the vitreous cavity, as well as peritumoral serous retinal detachment. The patient underwent left eyeball enucleation. The histopathological diagnosis was metastatic tubular adenocarcinoma involving the retina and choroid that partially infiltrated the sclera and the proximal optic nerve.

The present case highlights a rare pathological entity associated with variable therapeutic schemes and survival times and poor prognosis in patients with metastatic intraocular tumors due to colorectal adenocarcinoma.

To describe a novel technique of amniotic membrane (AM) patch graft in the management of double chamber treatment after big-bubble deep anterior lamellar keratoplasty (DALK).

A 35-year-old male patient with advanced keratoconus underwent bigbubble DALK. Manual lamellar dissection was done due to failed big-bubble. First-day postoperative double chamber was detected. Air bubbling and SF6 injection were tried without any success. Double chamber resolved by fixation of AM transplantation patch graft (1 × 1 mm) over the Descemet’s membrane perforation with fibrin glue.

Amniotic membrane patch graft can be used in the management of double chamber after DALK not responsive to intracameral gas injection.