[ ISSN : 3068-0743 ]
Glaucoma filtration surgeries; Anti-scarring drugs; Drug delivery systems; Mitomycin C; Transforming growth factor-?; Vascular endothelial growth factor; Gelatin hydrogel
Anti-scarring Drugs And Drug Delivery systems (DDSs) that are more effective and safer than mitomycin C have been sought to improve the outcome of glaucoma filtration surgeries. Drugs that selectively inhibit wound healing, including anti-transforming growth factor-β and anti-vascular endothelial growth factor antibodies, have been investigated, although their advantages are yet to be verified in humans. In addition, novel sustained release DDSs with fewer toxic effects have been studied for application after glaucoma surgeries. Several potential biomaterials for such DDSs, including gelatin hydrogel, have been introduced.
Sugiyama T. Application of Anti-Scarring Drugs and Drug Delivery Systems in Glaucoma Surgeries. SM Opthalmol J. 2015; 1(1): 1001
Application of mitomycin C (MMC) as an antimetabolite in glaucoma filtration surgeries, particularly trabeculectomy, has greatly improved surgical outcomes through suppression of fibroblast proliferation. However, application of MMC increases the risk for complications including infectious endopthalmitis [1-3], since MMC also affects cells unrelated to wound healing and may produce a vascular thin blebs. In order to address this issue, safer drugs for glaucoma surgeries have been sought in recent times. In addition, application of novel biomaterials to control scarring and/ or for sustained release of drugs has also been studied.
Drugs that selectively inhibit wound healing after glaucoma filtration surgeries, including anti-transforming growth factor (TGF) -β and anti-vascular endothelial growth factor (VEGF) antibodies, have been investigated. Human monoclonal antibody that neutralizes TGF-β2 (CAT 152; lerdelimumab) was one of the postoperative anti-scarring candidates in glaucoma surgery [4]. However, there was no difference between subconjunctival application of CAT-152 and placebo in preventing the failure of primary trabeculectomy in a phase III study [5]. As for the anti-VEGF antibody, the 6-month outcomes of a pilot clinical study with a small number of subjects (13 patients in each group) suggested that 3 subconjunctival injections of 0.125 mg of bevacizumab(0.05 mL) were successful in reducing intraocular pressure (IOP), compared to the conventional use of 0.03% MMC [6]. In this study, the first, second, and third subconjunctival injections of bevacizumab were administered immediately before surgery 5mm from the limbus in the same quadrant as the proposed trabeculectomy, immediately after surgery at the edge of the formed bleb, and on the 7th postoperative day 5mm from the sclerostomy site in the superior quadrant, respectively. However, a long-term study with a large number of patients is still needed to verify the effectiveness and safety of anti-VEGF antibodies. A Rho-associated protein kinase inhibitor, Y-27632, was reported to have profound effect on activities of human Tenon fibroblasts and prevent fibroproliferation and scar formation in a rabbit model of glaucoma surgery [7].
Moreover, other candidates have been investigated as anti-scarring agents in glaucoma filtration surgery: Pirfenidone (anti-fibrotic potential was already established in other organs such as the lung, liver, and kidney) [8], antisense oligodeoxynucletides for connexin 43 (a critical component of gap junctions) [9], ilomastat (a matrix metalloproteinase inhibitor) [10], tacrolimus (an immunosuppressive agent) [11], octreotide (a growth hormone inhibitor) [11], saratin (a platelet binding modulator) [12], P-glycoprotein blockers (verapamil, cyclosporine) [13], sonepcizumab, a humanized monoclonal antibody for sphingosine-1-phosphate (a regulator of tissue fibrosis) [14], simtuzumab, a humanized monoclonal antibody for lysyl oxidase-like 2 (a potential agent for pathologic angiogenesis, inflammation, and fibrosis) [15], Suc-Val-Pro-PheP (OPh)2, a chymase inhibitor [16,17]. Future clinical utilization of these agents is expected, although it is potentially challenging to verify their effects in human glaucoma surgeries.
Novel drug delivery systems (DDSs) have also been investigated for sustained drug release, since it is important to prevent scarring over an extended period following glaucoma surgeries. One such example is that of Ozurdex®, a polymer based sustained-release intravitreal DDS containing dexamethasone, currently approved by the United States Food and Drug Administration for the treatment of macular edema. Experiments with rabbits suggested that subconjunctival implantation of Ozurdex® prolonged bleb survival after glaucoma surgery, although this effect was not significant compared to that observed following conventional application of MMC [18]. Ologen® is another DDS comprising MMC soaked biodegradable collagen matrix and is clinically used in some Asian countries. Implantation of Ologen® resulted in comparatively stable IOP 12 months after glaucoma surgery. However, after the implantation, encapsulated blebs were generated at a more rapid pace than that observed after conventional trabeculectomy, mostly owing to the ability of Ologen® to induce a number of fibroblasts inside to move into a bleb. [19]. Other types of biomaterials, including freeze dried bilayered fibrin-binding amniotic membrane [20], microfilms composed of poly (DL-lactide-co-caprolactone) [21], and polymer polylactioglycolic acid films [22], have also been investigated for sustained release of anti-scarring drugs after glaucoma surgeries, although they are yet to be applied in humans.
Gelatin hydrogel (GH) is a biodegradable material developed in Japan and used as DDS for bioactive proteins in other fields of medicine [23]. Using GH, controlled release of bioactive growth factors, over the time range of 5 days to 3 months, was possible [24, 25]. Various growth factors, including basic fibroblast growth factor (bFGF) and TGF–β1, have been incorporated in GH, and their controlled release has been effective for regeneration therapy of various tissues [26,27]. For ophthalmological research, GH impregnated with bFGF has been used to induce experimental models of subretinalor corneal neovascularization [28,29]. On the other hand, our research group has recently investigated application of GH containing anti-scarring drugs (a chymase inhibitor, MMC) after glaucoma surgery [17,30]. The results suggested that GH loading MMC and conventional application of MMC produced comparable effects on IOP reduction and bleb formation; further, compared to eyes treated with MMC via the conventional route, GH-treated eyes had reduced toxicity to conjunctiva, particularly the vessels, probably because the concentration of MMC in contact with these eyes was less [30]. The use of new DDSs such as GH may reduce toxicity to the eye, particularly the conjunctiva.
In summary, utilization of new anti-scarring drugs and/or novel DDSs, which are more effective and safer than conventional application of MMC, is anticipated in the near future for better postoperative outcome with better bleb survival and lower rates of complications after glaucoma filtration surgeries
A 34-year-old man presented with binocular proptosis for half a year and sight lost for seven days. The patient had a facial lymphoma resection and postoperative chemotherapy five years ago.
Dajiang Wang¹ and Boyan Fang²*
Ocular diseases are devastating as most of them would cause irreversible visual impairment and blindness. Conceptually, cell replacement therapy with new ocular cells generated by ocular stem cells can substitute the degenerated or damaged cells in the diseased tissue. This concept has first been applied in the limbal transplantation by limbal progenitor cells. Unfortunately, patients with limbal stem cell deficiency and the endogenous progenitor cells present in human corneal endothelium as well as retina have limited regenerative power. In recent decades, other stem cell sources for ocular cell regeneration have been explored and are now feasible with the use of pluripotent stem cells, such as the embryonic stem cells (ESCs) and the induced pluripotent stem cells (iPSCs). Nevertheless, autologous transplantation would not be applicable using ESCs, whereas the variability of reprogramming methods as well as genetic instability of iPSCs has hindered their direct applications. Alternatively, human adult stem cells, such as hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are found throughout the body and can be efficiently isolated from patients while maintaining the characteristics of self-renewal and multipotency. Superiorly, adult stem cells harness the potential to protect the ocular cells, where MSCs are able to modulate the microenvironments of the diseased eye for neuroprotection. This article compiled the current progress of MSCs in ocular research. Moreover, the updated clinical trials of adult stem cells in ocular diseases are summarized. In addition, potential challenges and future prospects of stem cell research in ophthalmology would also be discussed.
Tsz Kin Ng* and Jasmine Sum-Yee Yung
Purpose: Choroidal neovascularization is a common complication following several retinal conditions, most commonly age-related macular degeneration (AMD). We present a case of bilateral extramacular choroidal neovascularization in a patient with wet AMD.
Methods/Patients: Interventional Case Report. Clinical, radiologic, and angiographic correlation.
Results: An 89 year old Caucasian male with Age-related Macular Degeneration (AMD) developed bilateral vitreous hemorrhages and subretinal hemorrhages after which were noted bilateral extramacular choroidal neovascular membranes. The vitreous hemorrhage in the left eye cleared on its own, while vitrectomy was performed in the right eye. Bevacizumab (Avastin) was injected into both eyes. Eighteen months after initial presentation and three months after Bevacizumab, the patient was asymptomatic, both neovascular membranes were inactive, and visual acuity had improved to 20/70 OD and 20/100 OS.
Conclusions: We report the first case of aggressive bilateral extramacular choroidal neovascular membranes in a patient with wet AMD. The pathophysiology that causes AMD to target the macula and fovea in most cases, but the extramacular region in this case, has yet to be elucidated.
Natasha A Naik*, Yannis M Paulus and Darius M Moshfeghi
Objective: To describe the method of Intraocular lens (IOL) power calculation in eyes after Intracorneal Ring Segment (ICRS) surgery for the treatment of post-LASIK ectasia.
Design: Retrospective observational case-series.
Participants: Three eyes of 2 patients were included in this study.
Methods: Corneal curvature in the central effective optical zone was averaged using corneal topography and k-reading (Kr) was calculated using Jarade IR method for Kr after LASIK. The calculated Kr was used in SRK-T formula for IOL calculation. Accuracy of this IOL calculation method was judged using the manifest refraction outcome after cataract surgery. All eyes were targeted for emmetropia after cataract.
Results: In our series, one eye developed cataract after ICRS surgery for the treatment of ectasia after hyperopic LASIK (+4 D) and 2 eyes developed cataract after ICRS surgery for the treatment of ectasia after myoic LASIK (-10 D). The spherical equivalent of manifest refraction after cataract surgery was within 1.25 D in all eyes.
Conclusion: Using the average corneal curvature in the central effective optical zone to calculate Kr “by Jarade IR” method was found to be accurate in calculating IOL power in ectatic eyes treated by ICRS surgery
Elias Jarade¹#, Ali Dirani¹,²#, Ali Fadlallah MD¹,², Elias Chelala², Henry Fakhoury¹, George Cherfan¹*
Purpose: Choroidal osteoma is a rare tumor which features intraocular bone formation. This tumor can be complicated by choroidal neovascularization which is a cause of impaired vision in this condition. We present a case of choroidal osteoma with choroidal neovascularization as a complication.
Methods: Case report with clinical and angiographic correlation.
Results: A 16 year old female presented with a choroidal osteoma in the left eye complicated by choroidal neovascularization. The patient was treated with Bevacizumab; an intravitreal anti-Vascular Endothelial Growth Factor (Anti-VEGF). Following treatment there was improvement in vision as well as resolution of the choroidal neovascular membrane.
Conclusion: We present a case of choroidal osteoma with choroidal neovascular membranes. Subfoveal Choroidal Neovascularization (CNV) associated with choroidal osteoma may be safely treated with bevacizumab. Larger studies are required to fully evaluate the management and long-term outcomes of anti-VEGF therapy for CNV associated with choroidal osteoma.
Courtney M Crawford¹ and Okezie C Igboeli²*
Infliximab is a chimeric monoclonal antibody against Tumor Necrosis Factor-α (TNF-α), initially developed for treatment of rheumatoid arthritis and inflammatory bowel disease
Es Souiri J¹, Abourazzak FE¹, Andaloussi Idrissi B² and Harzy T¹*
Purpose: To evaluate etiologies, management, and outcomes of patients with Giant Retinal Tears (GRT) undergoing primary surgery at tertiary referral center.
Methods: A Retrospective, consecutive case series of 94 patients with at least 3 months follow up after silicon oil removal. 57 eyes (60.6%) underwent vitrectomy, 36 eyes (38.3%) underwent combined vitrectomy with buckling and 1 eye (1.1%) underwent scleral buckling. Perfluorocarbon (PFCL) heavy liquid to flatten GRT f lap intraoperative has been used then PFCL air exchange then air silicon exchange in all eyes undergoing vitrectomy. Fellow eye was observed for retinal detachment.
Results: Idiopathic cause constitute 47 eyes (50%), 25 eyes (26.6%) are myopic and 22 eyes (23.4%) have history of trauma. 85 eyes (90.4%) achieved anatomic success. Visual acuity at the last follow-up was at least 20/400 in 71 eyes (75.5%) of patients. Recurrent retinal detachment after Silicon Oil Removal (SOR) was found in 21 eyes (22.3%) of which, 50% had Proliferative Vitreoretinopathy Grade C (PVR-C) or more (p value 0.03) and 20% had GRT size more than 180° (p value 0.04). Pars Plana Vitrectomy (PPV) alone (p value 0.89) or combined PPV with buckling (p value 0.98) have no significant correlation with recurrent Retinal Detachment (RD). 21% of the fellow eye had retinal detachment.
Conclusion: Idiopathic cause constitutes the majority 50%. Patients with GRT who underwent surgery achieved high anatomic success rate. PVR-C or more remain the most significant risk factor for recurrent RD after SOR whereas PPV alone or combined PPV with buckling have no significant correlation with recurrent RD.
Eman Abo Taleb
Purpose: To report the efficacy of Ocriplasmin in the treatment of small-medium sized idiopathic full thickness Macular Holes with focal Vitreomacular traction in comparison with vitreous surgery.
Methods: Retrospective observational single-centre small case series (n=6) studythat included patients who underwent vitrectomy after unsuccessful treatment ofsmall-medium size full thickness Idiopathic macular holes with ocriplasmin.
Results: 6 eyes with full-thickness macular holes and VMT were included, whereby in 4 eyes an epiretinal membrane was present (66.7%). Resolution of VMT after intravitreal injection of ocriplasmin was shown in three out of six eyes (50%) and in all six eyes after vitrectomy (100%). Of all six eyes presenting macular holes with a mean size of 265 µm ± 109 µm at baseline visit, five eyes showed persistent macular holes at the second follow-up visit with a mean size of 335 µm ± 166 µm. After vitrectomy no macular hole could be detected at the f inal follow-up visit.
Conclusion: We present our clinical experience with intravitreous injection of Ocriplasmin to confirm the presumed therapeutic effect in patients suffering from Vitreomacular Traction (VMT) with small-medium sizedfull thickness Macular holes (MH). Small macular holes could frequently be closed with only Ocriplasmin and without surgery with a 17% closure rate. Enlargement in all holes that failed to close with Ocriplasmin was observed in all treated eyes which makes us believe that the VMT could have a Protective role. Ellipsoid zone disruptions were evident in 50% of treated eyes and more common in eyes with successful VMT release. Although data on Ocriplasmin from several studies remain controversial but so far the results are consistent with the results and recommendations of other clinical studies and the European Medicine Agency. We agree that replacing vitrectomy for MHs with one injection of Ocriplasmin would be a very attractive option but so far Pars plana vitrectomy remain the treatment of choice for most eyes with MHs. Further Work is recommended to reveal the Cause of the ellipsoid zone Changes, the mechanisms of tractional forces and to investigate the Long term side effects of Ocriplasmin.
Khaled Helaiwa¹,², Ammar Heider², KU Bartz-Schmidt¹ and Kai Januschowski¹,²*
Purpose: To analyze and compare the refractive outcomes of standard phacoemulsification with femtosecond laser-assisted cataract surgery performed during the initial learning curve and a year later by experienced surgeons.
Methods: This single-center retrospective study was divided into 3 groups: Group 1, 63 patients who underwent standard phacoemulsification (control group) prior to femtosecond laser acquisition by two anterior segment surgeons; Group 2, the first 104 patients who underwent femtosecond laser-assisted cataract surgery by the same surgeons from Feb 19, 2014 to April 30, 2014 (learning curve group) and Group 3,108 patients who underwent femtosecond laser-assisted cataract surgery by the same surgeons a year later from Feb, 2015 until June 30, 2015 (experienced group).
Results: Mean absolute refraction prediction errors were 0.37 ± 0.25 Diopters (D) in the control group, 0.30 ± 0.24 D in the “learning group” and 0.30 ± 0.24 D in the experienced group with no significant differences among groups. The percentages of eyes within 0.5 D of the targeted refraction were 69.8%, 90.5% and 82.5% in the control group, learning group, and experienced group, respectively (p
Conclusion: There was no statistically significant difference in the mean postoperative refraction prediction errors between femtosecond laser-assisted cataract surgery and standard phacoemulsification in either the learning curve or experienced group. However, a higher percentage of patients were within 0.5 D of the targeted refraction in the learning curve femtosecond laser-assisted cataract surgery group compared with the standard phacoemulsification group.
Ildamaris Montes de Oca, Sumitra S Khandelwal, Eric J Kim, Tim Soeken, Ryan Barrett, Li Wang, Mitchell P Weikert, Douglas D Koch and Zaina Al-Mohtaseb*
Scleral fixated Intraocular Lenses (IOLs) have grown in popularity as an effective solution to aphakic eyes with insufficient capsular support. A rare but debilitating complication includes development of Uveitis-Glaucoma Hyphema (UGH) syndrome. Recurrent hemorrhages with UGH syndrome are even more unusual (UGH-Plus syndrome). Classically, this syndrome develops following anterior chamber IOLs, but the literature is scarce with reference to UGH-Plus syndrome after posterior chamber IOL implantation. We present two cases of patients with scleral-tunneled IOLs who developed UGH-Plus syndromeresulting from haptic interference with ciliary body vessels. We describetwo different IOL sparing management approaches including introduction of a novel surgical solution.
Crystal Le, Lena Al-Dujaili and Ramesh Ayyala*