Automated machine learning-based classification of proliferative and non-proliferative diabetic retinopathy using optical coherence tomography angiography vascular density maps.

PURPOSE: The study aims to classify the eyes with proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR) based on the optical coherence tomography angiography (OCTA) vascular density maps using a supervised machine learning algorithm. METHODS: OCTA vascular density maps (at superficial capillary plexus (SCP), deep capillary plexus (DCP), and total retina (R) levels) of 148 eyes from 78 patients with diabetic retinopathy (45 PDR and 103 NPDR) was used to classify the images to NPDR and PDR groups based on a supervised machine learning algorithm known as the support vector machine (SVM) classifier optimized by a genetic evolutionary algorithm. RESULTS: The implemented algorithm in three different models reached up to 85% accuracy in classifying PDR and NPDR in all three levels of vascular density maps. The deep retinal layer vascular density map demonstrated the best performance with a 90% accuracy in discriminating between PDR and NPDR. CONCLUSIONS: The current study on a limited number of patients with diabetic retinopathy demonstrated that a supervised machine learning-based method known as SVM can be used to differentiate PDR and NPDR patients using OCTA vascular density maps.

Multifocal electroretinogram in diabetic macular edema and its correlation with different optical coherence tomography features.

PURPOSE: To evaluate multifocal electroretinogram (mfERG) parameters in eyes with diabetic macular edema (DME) and its correlation with vision and optical coherence tomography (OCT) features. METHODS: Fifty-four eyes of 27 subjects with DME due to nonproliferative diabetic retinopathy were evaluated. MfERG responses were measured in three concentric rings. Macular thickness was measured by OCT in each segment of the three concentric rings, and mfERG rings were superimposed on the macular thickness map. The correlation between macular thickness in specific points of the thickness map and changes of the mfERG parameters in the corresponding points of the mfERG field map was evaluated and the relationship between the OCT and mfERG changes and changes of best-corrected visual acuity (BCVA) was investigated. The central foveal B-scans of SD-OCT were used to evaluate any correlation between the external limiting membrane (ELM) status, ellipsoid zone (EZ) status, presence of cysts or disorganization of retinal inner layers (DRIL), and mfERG parameters at the central corresponding area. RESULTS: The mean of BCVA was 0.5 ± 0.3 in logMAR, and the central macular thickness was 392.6 ± 123.4 microns. The central ring P1 and N2 amplitudes had a significant correlation with BCVA in univariate and multivariate analyses (P = 0.001 for both, r = - 0.346 and r = - 0.646, respectively). There was a significant correlation between retinal thickness and the N1 amplitude in the central ring (P = 0.02, r = - 0.343). Outer retinal layer disruption (ELM and EZ) correlated with prolonged P1 implicit time at the corresponding location (P = 0.005, r = 0.068). The presence of the DRIL was associated with reduced P1 and N2 amplitudes (P = 0.037, r = - 0.284 and P = 0.019, r = - 0.562, respectively). A significant correlation was also found between the presence of cysts and a lower central P1 amplitude (P = 0.033, r = - 0.376). CONCLUSION: In diabetic patients, discrete changes of some parameters in the central ring of the mfERG field map (e.g., P1 and N2 amplitudes) have a significant correlation with both structural OCT abnormalities in the corresponding points of the thickness map (like DRIL, intraretinal cyst and ELM/EZ disruption) and BCVA. Predictive models such as those described in this report may make it possible to identify the relationship between specific anatomical and functional characteristics in diabetic retinopathy.

Intravitreal bevacizumab alone or combined with 1 mg triamcinolone in diabetic macular edema: a randomized clinical trial.

PURPOSE: To compare the results of intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal 1 mg triamcinolone acetonide (IVT) in center-involved diabetic macular edema. METHODS: In this randomized clinical trial study, ninety-two eyes of 46 patients with bilateral center-involved diabetic macular edema and no previous treatment were included in the study. One eye of each patient was randomly assigned to 1.25 mg of IVB injection or combination of 1.25 IVB and 1 mg IVT. Evaluation of best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP) and grading of lens opacity was conducted at baseline, and weeks 2, 4, 6, 8, 12 and 24 after treatment. Retreatment was performed at a 6-week interval whenever indicated based on CMT. RESULTS: Between the groups, BCVA changes were not statistically different until 24-week follow-up (P > 0.05), but at 24 weeks after treatment, BCVA improvement was significantly better in IVB group (P = 0.049). Significant CMT reduction was observed in each group along the follow-up period (P = 0.001). The mean CMT reduction was more significant in combination (IVB + IVT) group at 2 weeks of follow-up (P < 0.001), but CMT changes were not significant between the groups at weeks 12th and 24th after injection. Overall, retreatment was applied for 59 eyes up to 24 weeks (33 in the IVB group, 26 in the IVB + IVT group). Among patients with 2 or more injections, number of injections was significantly lower in IVB + IVT group (P = 0.043). Three eyes within IVB + IVT group developed IOP rise beyond 21 mmHg, which were controlled with topical anti-glaucoma medications within 1 week. Changes in lens opacity were not significant between two groups. CONCLUSION: Eyes treated with IVB plus 1 mg IVT injections had more significant reduction in CMT in early post-injection, but this effect was transient. Although after 24 weeks visual acuity improvement was better in IVB group, combination therapy may decrease the number of injections. Combining 1 mg of intravitreal triamcinolone with bevacizumab was not accompanied with significant side effects.

CHOROIDAL THICKNESS CHANGES IN PROLIFERATIVE DIABETIC RETINOPATHY TREATED WITH PANRETINAL PHOTOCOAGULATION VERSUS PANRETINAL PHOTOCOAGULATION WITH INTRAVITREAL BEVACIZUMAB.

PURPOSE: To compare choroidal thickness (CT) and retinal thickness (RT) between eyes with proliferative diabetic retinopathy treated with panretinal photocoagulation (PRP) or PRP with intravitreal bevacizumab (PRP + IVB). METHODS: Thirty-three patients with proliferative diabetic retinopathy were randomized to have one eye treated with PRP and the other with PRP + IVB. Change in CT was compared with baseline using enhanced depth imaging-optical coherence tomography at baseline and Months 1, 3, 6, and 10 after treatment. Change in RT was similarly assessed using spectral domain optical coherence tomography. Changes in both CT and RT were assessed in all nine macular areas as defined by Early Treatment Diabetic Retinopathy Study subfields. RESULTS: The PRP + IVB group had a significant decrease in subfoveal CT at 3 and 10 months (323.9 ± 62 µm at baseline vs. 320.7 ± 64.8 µm at Month 3 [P = 0.024] and 304.7 ± 65.6 µm at Month 10 [P = 0.003]). Subfoveal CT significantly decreased at 10 months compared with baseline in the PRP group (320.8 ± 57.7 at baseline to 297 ± 66.3 µm at 10 months, P = 0.01). Subfoveal CT was not significantly different between the 2 groups at 10 months. The best-corrected visual acuity did not change after treatment in the two groups, and there was no correlation between BCVA and CT changes (r = 0.222, P = 0.37 in the PRP group and r = 0.387, P = 0.12 in the PRP + IVB group). Significant increases in RT were seen in the PRP + IVB group at 6 months and in the PRP group at Months 1, 3, 6, and 10. A correlation between changes in CT and RT was only seen in the PRP group at 10 months after treatment. CONCLUSION: Eyes with proliferative diabetic retinopathy treated with PRP + IVB and PRP both had significant reduction in CT at 10 months; however, the eyes that were also treated with IVB also underwent an earlier but transient reduction at 3 months. Patients treated with IVB underwent less increase in RT.

Comparison of Refractive Error Changes in Retinopathy of Prematurity Patients Treated with Diode and Red Lasers.

AIM: To compare refractive error changes in retinopathy of prematurity (ROP) patients treated with diode and red lasers. METHODS: A randomized double-masked clinical trial was performed, and infants with threshold or prethreshold type 1 ROP were assigned to red or diode laser groups. Gestational age, birth weight, pretreatment cycloplegic refraction, time of treatment, disease stage, zone and disease severity were recorded. Patients received either red or diode laser treatment and were regularly followed up for retina assessment and refraction. The information at month 12 of corrected age was considered for comparison. RESULTS: One hundred and fifty eyes of 75 infants were enrolled in the study. Seventy-four eyes received diode and 76 red laser therapy. The mean gestational age and birth weight of the infants were 28.6 ± 3.2 weeks and 1,441 ± 491 g, respectively. The mean baseline refractive error was +2.3 ± 1.7 dpt. Posttreatment refraction showed a significant myopic shift (mean 2.6 ± 2.0 dpt) with significant difference between the two groups (p < 0.001). There was a greater myopic shift among children with zone I and diode laser treatment (mean 6.00 dpt) and a lesser shift among children with zone II and red laser treatment (mean 1.12 dpt). The linear regression model, using the generalized estimating equation method, showed that the type of laser used has a significant effect on myopic shift even after adjustment for other variables. CONCLUSION: Myopic shift in laser-treated ROP patients is related to the type of laser used and the involved zone. Red laser seems to cause less myopic shift than diode laser, and those with zone I involvement have a greater myopic shift than those with ROP in zone II.

Intravitreal bevacizumab in retinopathy of prematurity: an interventional case series.

BACKGROUND: To evaluate the results of intravitreal bevacizumab in terms of regression of retinopathy of prematurity (ROP). METHODS: In this interventional case series, 12 eyes from January 2007 to December 2008 were included. Two groups of patients were considered. Group 1 included those ROP patients who did not respond to conventional laser therapy within 3 weeks or had some complications (hyphema or vitreous hemorrhage) after conventional laser therapy; intravitreal injection (0.625 mg) was performed as an adjuvant therapy. Group 2 included those with aggressive posterior ROP who received single intravitreal bevacizumab injection as the initial treatment. RESULTS: Ten eyes of 12 patients with mean gestational age of 28.5 (range: 26-32) weeks and birth weight of 1,218 grams (range: 900-1,630) were included in the study. Mean conceptional age at the time of first visit was 40 weeks (30-48 weeks). All the patients had a history of supplemental oxygen. Eight patients (26.3%) were under mechanical ventilation. Eight eyes received bevacizumab after conventional laser therapy (group 1). Four eyes received intravitreal bevacizumab as the initial therapy (group 2). All of the patients were followed up for at least 1 year. All patients in group 1 responded to this adjuvant (intravitreal bevacizumab) treatment within 1 week, but two eyes of group 2 needed laser therapy 1.5 month after intravitreal bevacizumab injection in spite of the initial treatment response. No complications such as cataract, endophthalmitis or retinal detachment occurred. CONCLUSIONS: The use of intravitreal bevacizumab injection in premature eyes was well-tolerated, and induced prompt regression as an adjuvant therapy after conventional laser therapy and also as an alternative therapy in the management of aggressive retinopathy of prematurity.

Intravitreal bevacizumab versus combined intravitreal bevacizumab and triamcinolone for neovascular age-related macular degeneration: six-month results of a randomized clinical trial.

PURPOSE: To determine whether combined intravitreal bevacizumab (IVB) and triamcinolone (IVT) is more effective than IVB alone in neovascular age-related macular degeneration. METHODS: This was a prospective, randomized clinical trial performed at two centers. Eligible eyes were assigned randomly to one of the two study arms. In the IVB group, 3 consecutive injections of 1.25 mg of bevacizumab were given 6 weeks apart, while in the IVB/IVT group, the first of the triple IVB injections was combined with 2 mg of IVB. A fourth IVB was injected in eyes demonstrating active choroidal neovascularization at Week 24. RESULTS: Sixty and 55 eyes were in the IVB and IVB/IVT groups, respectively. Best-corrected visual acuity improved, and central macular thickness was reduced significantly in both groups at all time points. Visual improvement was more pronounced in the IVB/IVT group compared with the IVB group 6 weeks (8.5 ± 14.4 vs. 3.8 ± 8.9 letters, P = 0.04) and 12 weeks (11.8 ± 16.6 vs. 6.2 ± 10.8 letters, P = 0.03) after initiation of therapy. However, there was no significant difference in visual improvement at Week 24 (11.3 ± 17.2 letters in the IVB/IVT group vs. 8.7 ± 15.6 letters in the IVB group, P = 0.40). The IVB/IVT group showed significantly less need for a fourth injection at Week 24 (34.5% vs. 53.3% in the IVB/IVT and IVB groups, respectively, P = 0.04). CONCLUSION: Mandated therapy with IVB improved best-corrected visual acuity and decreased central macular thickness in neovascular age-related macular degeneration. The addition of low-dose IVT temporarily increased the therapeutic efficacy in the early postinjection period and resulted in fewer requirements for repeat IVB injections at 6 months; however, final levels of visual improvement were comparable in the 2 study groups.

Effect of panretinal photocoagulation on macular vasculature using optical coherence tomography angiography.

BACKGROUND: To evaluate the changes of macular vascular density in the superficial capillary (SCP) and the deep capillary plexus (DCP), foveal avascular area (FAZ), choroidal flow, and macular thickness after pan-retinal photocoagulation (PRP). METHODS: In this prospective interventional non-comparative case series, patients with very severe nonproliferative (NPDR) and early proliferative diabetic retinopathy (PDR) and no significant macular edema who were candidates for pan-retinal photocoagulation underwent measurement of corrected distance visual acuity (CDVA), optical coherence tomography (OCT), Optical coherence tomography angiography (OCTA) at the baseline, 1, and 6 months following completion of PRP treatment. RESULTS: Thirty-nine eyes from 21 patients with diabetes were enrolled. Superficial and deep capillary plexus densities in the foveal and parafoveal area didn't change significantly 1 and 6 months post-PRP (p > 0.1 in all of them). The FAZ area constricted 6 months following PRP (p = 0.075). Based on the calculated circularity index, the FAZ became significantly more circular after 6 months of follow-up (p = 0.047). Although the choroidal flow area increased after PRP this increase wasn't statically significant neither at 1 month nor at 6 months post-PRP (p = 0.31 and 0.23, respectively). CONCLUSION: Although OCTA parameters were not significantly affected by PRP at both short-term (1 month) and long-term (6 months) follow-ups, the FAZ area became significantly circular after PRP may be due to redistribution of blood flow in hypoperfused foveal capillary plexus.

Retinal image mosaicking using scale-invariant feature transformation feature descriptors and Voronoi diagram.

Purpose: Peripheral retinal lesions substantially increase the risk of diabetic retinopathy and retinopathy of prematurity. The peripheral changes can be visualized in wide field imaging, which is obtained by combining multiple images with an overlapping field of view using mosaicking methods. However, a robust and accurate registration of mosaicking techniques for normal angle fundus cameras is still a challenge due to the random selection of matching points and execution time. We propose a method of retinal image mosaicking based on scale-invariant feature transformation (SIFT) feature descriptor and Voronoi diagram. Approach: In our method, the SIFT algorithm is used to describe local features in the input images. Then the input images are subdivided into regions based on the Voronoi method. Each pair of Voronoi regions is matched by the method zero mean normalized cross correlation. After matching, the retinal images are mapped into the same coordinate system to form a mosaic image. The success rate and the mean registration error (RE) of our method were compared with those of other state-of-the-art methods for the P category of the fundus image registration database. Results: Experimental results show that the proposed method accurately registered 42% of retinal image pairs with a mean RE of 3.040 pixels, while a lower success rate was observed in the other four state-of-the-art retinal image registration methods GDB-ICP (33%), Harris-PIIFD (0%), HM-2016 (0%), and HM-2017 (2%). Conclusions: The proposed method outperforms state-of-the-art methods in terms of quality and running time and reduces the computational complexity.

Erratum: Retinal image mosaicking using scale-invariant feature transformation feature descriptors and Voronoi diagram (Erratum).

[This corrects the article DOI: 10.1117/1.JMI.7.4.044001.].

Intravitreal Ziv-Aflibercept in Patients With Diabetic Macular Edema Refractory to Intravitreal Bevacizumab.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of intravitreal ziv-aflibercept (IVZ) in patients with diabetic macular edema (DME) resistant to intravitreal bevacizumab (IVB). PATIENTS AND METHODS: This prospective study was conducted in patients with persistent DME. Patients were switched to IVZ no longer than 6 weeks after the last three consecutive monthly IVB treatments and monitored over a course of 12 weeks. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and macular volume on optical coherence tomography were compared. RESULTS: A total of 59 eyes (38 patients) were included. Mean BCVA improved from 0.84 to 0.71 logMAR (P = .001) after first IVZ treatment and remained significant. In a subgroup analysis, this significance was observed only in the group with baseline visual acuity of less than 20/50. Mean CMT decreased from 479 µm to 364 µm (P = .004) after the first IVZ injections and remained significant. CONCLUSION: IVZ may be best reserved for patients with persistent DME after initial failure with bevacizumab, with less likelihood for anatomic or functional improvement in those with mild persistent DME. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:145-151.].

Effects of intravitreal morphine administered at different time points after reperfusion in a rabbit model of ischemic retinopathy.

PURPOSE: To investigate the effects of morphine administered after reperfusion in a rabbit model of ischemic retinopathy. METHODS: The right eyes of 54 albino New Zealand rabbits were randomly allocated into nine treatment groups (n = 6 in each group). The eyes in saline-control group received 0.1 mL of phosphate-buffered saline solution intravitreally. In the ischemia-saline group, ischemia was induced by raising the intraocular pressure to 150 mmHg for 60 minutes. Then 0.1 mL of phosphate-buffered saline solution was administered intravitreally 5 minutes after reperfusion. The eyes in three ischemia-morphine groups (ischemia-morphine 0 hour, 1 hour, and 18 hours) received 0.1 mL of morphine (10 micromol/L) intravitreally 5 minutes, 1 hour, or 18 hours after termination of 60 minutes of ischemia, respectively. The eyes in ischemia-naloxone-morphine group received 0.05 mL of naloxone (10 micromol/L) intravitreally followed by injection of 0.05 mL morphine (10 micromol/L) 5 minutes after termination of ischemia. Toxicity controls were performed with morphine (10 micromol/L) and naloxone (10 micromol/L) without ischemia. Histologic evaluation was performed for all groups on the seventh postoperative day. RESULTS: Sixty minutes of ischemia led to severe cell loss in ganglion cell layer and thinning of the inner nuclear layer in ischemia-saline group compared with that of the saline-control group (P < 0.001). Thickness of the inner plexiform layer to the inner limiting membrane (a measure of inner retinal thickness) was significantly increased due to edema (P < 0.001). Administration of morphine 5 minutes after reperfusion significantly improved all of the above mentioned indices compared with ischemia-saline group (P < 0.001). Administration of morphine 1 hour after reperfusion had also a significant effect on the improvement of above mentioned indices compared with saline-control group (P < 0.05). However, the number of ganglion cells was significantly higher in ischemia-morphine 0 hour group compared with ischemia-morphine 1 hour group (P < 0.001). Morphine treatment 18 hours after reperfusion did not change the amount of injury. Administration of naloxone 5 minutes before morphine abolished most of the morphine protective effects. CONCLUSION: Intravitreal administration of morphine immediately after reperfusion maximally protects retina against ischemia-reperfusion injury. Pharmacologic evidence suggests that this protective phenomenon may be mediated in part by opioid receptors.

Prevalence and Risk Factors of Retinopathy of Prematurity in Iran.

PURPOSE: The present study aimed to evaluate the frequency and risk factors of retinopathy of prematurity (ROP) among Iranian infants. METHODS: A retrospective cohort study was conducted on infants who had undergone screening for ROP at Farabi Eye Hospital, between March 2016 and March 2017. Data were analyzed based on the presence of extreme prematurity (gestational age ≤ 28 weeks), extremely low-birth-weight ( ≤ 1000 g), and multiple-gestation (MG) infants. RESULTS: The prevalence of ROP was 27.28% ( n = 543) among all screened infants, 74.4% for extremely preterm (EP) infants, 77.5% for extremely low birth weight (ELBW) babies, and 27.25% for infants from MG pregnancies. On multivariate analysis, gestational age, birth weight, and history of transfusion ( P < 0.0001, P < 0.0001, and P = 0.04, respectively) were found to be significantly associated with ROP. More advanced stages of ROP ( P < 0.0001) were observed in EP and ELBW infants. Birth weight ( P = 0.088), history of transfusion ( P = 0.066), and intubation ( P = 0.053) were not associated with increased risk of ROP in EP infants, while gestational age ( P = 0.037) and history of transfusion ( P = 0.040) were significant risk factors for ROP in ELBW infants. Gestational age (P < 0.001) and birth weight ( P = 0.001) were significantly associated with ROP in infants from MG pregnancies in multivariate analysis. CONCLUSION: ROP remains a commonly encountered disease, especially in ELBW and EP infants. The history of transfusion may have a role in stratifying the risk for ROP and guiding future screening guidelines.

The Accuracy of Digital Imaging in Diagnosis of Retinopathy of Prematurity in Iran: A Pilot Study.

PURPOSE: To evaluate sensitivity and specificity of digital retinal image reading in the diagnosis of referral-warranted retinopathy of prematurity (ROP). METHODS: Infants referred to the ROP clinic underwent fundus examination through indirect ophthalmoscopy. Fundus photographs were acquired using RetCam (shuttle 2; Clarity medical systems, Pleasanton, CA, USA). Four retinal specialists who were blind to patients' information reviewed the RetCam fundus photographs. By comparing the results of photographs' readings with that of indirect ophthalmoscopy as the gold standard, the sensitivity and specificity of telescreening was determined. RESULTS: A total of 147 treatment-naïve patients met the inclusion criteria and were enrolled in the study. Mean gestational age (GA) was 28.6 ± 2.0 weeks. Digital retinal imaging had sensitivity of 85% and specificity of 35% in detecting referral-warranted ROP in our study. Positive predictive value of digital photography was 80%, and negative predictive value was 43%. CONCLUSION: Digital photography for diagnosis of ROP may show good potential as a screening modality in developing countries. It can facilitate early diagnosis, prevent unnecessary referrals, and be implemented for investigational purpose. However, the overall study result did not provide evidence to propose digital photography as a substitute for indirect ophthalmoscopy in the diagnosis of ROP.

Incidence and Risk Factors for Post-Intravitreal Injection Endophthalmitis in a Modified Operating Room Setting.

Purpose: To evaluate the incidence and risk factors of post-intravitreal injection (IVI) endophthalmitis in a single center modified operating room (OR) setting.Methods: In a retrospective chart review study, patients who underwent IVI in a modified OR between September 2014 and November 2016 were included. Cases of post-IVI endophthalmitis were identified from the Hospital Infection Control Committee records, which tracks all post-procedure infections.Results: 51 472 IVIs (37 814 patients) including 13 658 bilateral simultaneous injections were performed during the study period. There were 17 cases of endophthalmitis (0.033%, 95% CI 0.019%-0.052%). There were no cases of bilateral endophthalmitis. Age, sex, indication for IVI, simultaneous bilateral injections, number of previous injections, and type of injected drug were not significantly associated with incidence of endophthalmitis.Conclusion: Post-IVI endophthalmitis is rare in this modified OR setting. Simultaneous bilateral IVIs and on-site preparation of injections are safe under these conditions.

Efficacy of Intravitreal Bevacizumab for the Treatment of Zone I Type 1 Retinopathy of Prematurity.

PURPOSE: To describe the efficacy of intravitreal bevacizumab for the treatment of type 1 retinopathy of prematurity (ROP) in zone I. METHODS: Preterm infants with type 1 ROP in zone I (zone I ROP, any stage with plus disease or zone I ROP, stage 3 without plus disease) were enrolled in this prospective study. Intravitreal bevacizumab (0.625 mg/0.025 ml) was injected under topical anesthesia. Patients were followed weekly for 4 weeks and then biweekly till 90 weeks gestational age. RESULTS: Seventy eyes of 35 patients with type 1 ROP in zone I were enrolled. At a gestational age of 90 weeks, ROP regressed with complete or near-complete peripheral retinal vascularization, in 82.9% of eyes after a single injection and in 92.9% of eyes after up to two injections. In five eyes (7.1%), ROP progressed to stage 4B or 5, so surgical management was required. There were no major complications such as endophthalmitis, cataract, or vitreous hemorrhage after injection. CONCLUSION: Intravitreal bevacizumab injection is an effective method for the management of patients with Zone I ROP requiring treatment; however, some cases may progress to more advanced stages and require surgical management. Close monitoring for recurrence or progression is necessary. Eyes with persistent zone I ROP may progress to advanced stages when treated with intravitreal bevacizumab injection and re-treatment may be needed.

Fibrin gel as a scaffold for photoreceptor cells differentiation from conjunctiva mesenchymal stem cells in retina tissue engineering.

Stem cell-based therapies are attraction approaches for regenerative medicine for treating retinal diseases. One of the limitations in cell therapy is cell death following post-injection whit preventing functional integration with retinal tissue. Fibrin gel, a bio-polymeric material with excellent biocompatibility, provides numerous advantages as a tissue engineering scaffold and a stem cell carrier. Therefore, current research is focusing on developing fibrin hydrogel scaffolds to protect stem cells during delivery and to stimulate endogenous regeneration through interactions of transplanted stem cells and retinal tissue. In this study fibrin gel was used as hydrogel scaffold for immobilization of cells. The structural characteristics of fibrin gel scaffold were examined with SEM. Rheological properties of fibrin gel were measured by rheometer and biodegradation rate of fibrin were assayed for 2 weeks. After isolation of stem cells CJMSCs, the cells were differentiated into photoreceptor-like cells by exposing with taurin for 14 days in tissue culture plate (TCP group) and fibrin hydrogel (3 D group). The attachment of cells was analyzed with SEM and MTT. The expression of rhodopsin, PKC, CRX, recoverin, peripherin, nestin and RPE65 as photoreceptor-like cell markers was evaluated by immunocytochemistry and quantitative real-time PCR (RT-PCR) in TCP and 3 D groups. The results of SEM analysis showed CJMSCs were well attached in fibrin gels and there were good integrity between cells and scaffold. The elastic modulus and constant degradation of the gel contributes to the growth and proliferation of cells. There was no toxicity effect of fibrin hydrogel on cells and the viability of cultured cells was higher in 3 D fibrin gels in comparison with TCP groups. After 2 weeks, the expression of rhodopsin, PKC, CRX, peripherin, recoverin, nestin and RPE65 as special markers of photoreceptor cells were detected by Real time PCR and immunofluorescence that these expressions in 3 D groups were higher than TCP groups. In conclusion, our findings showed that application of readily available sources of adult stem cells like human conjunctiva stem cells encapsulated in fibrin gel could be interesting strategy to enhance photoreceptor progenitor cell numbers for repair and regeneration of retina disease such as photoreceptor injury.

Comparison of Intravitreal Bevacizumab and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity.

PURPOSE: To compare the outcomes of patients with type I retinopathy of prematurity (ROP) treated with either intravitreal bevacizumab (IVB) or retinal laser photocoagulation (RLP). DESIGN: Retrospective case series. PARTICIPANTS: Infants treated for type I ROP with IVB or RLP. METHODS: Patients who were born between January 2011 and December 2014 and were treated in Farabi Eye Hospital were included. The outcomes were stratified and analyzed, based on the treatment type and ROP zone. MAIN OUTCOME MEASURES: Need for retreatment, time to regression, refractive errors, retinal adverse anatomic outcomes, and rate of complications. RESULTS: Five hundred twenty-three patients were treated for type 1 ROP, of whom 493 (986 eyes) met inclusion criteria. Seven hundred twenty-four eyes (73.4%) received IVB, and 262 eyes (26.5%) received RLP. Re-treatment (because of recurrent or persistent retinopathy) occurred in 14.4% (106/724) of eyes initially treated with IVB and in 8.8% (23/262) eyes initially treated with RLP (P = 0.065). Re-treatment was not significantly different between the 2 groups for patients with zone I disease (P = 0.978). Re-treatment rate was considerably higher in patients with zone II disease treated with IVB (69/558 [12.3%]) compared with those treated with RLP (20/251 [7.9%]; P = 0.017). In the IVB group, 82.8% and 53.4% of eyes showed an avascular area in zone III (despite ROP regression) at 1 and 2 years after treatment, respectively. The spherical power and the spherical equivalent were significantly higher in eyes treated with RLP (-1.31±2.83 diopters [D] and -2.84±2.77 D, respectively) than eyes treated with IVB (0.19±3.21 D and -1.26±3.19 D, respectively; P = 0.016 and P = 0.007, respectively). Differences in astigmatic power were not significant. CONCLUSIONS: Both IVB and RLP are effective treatments for type 1 ROP. Longer follow-up time is necessary for infants treated with IVB. More patients with zone II disease treated with RLP achieved disease regression after a single treatment than those who received IVB, although outcomes after re-treatment were comparable except for a greater refractive error in patients treated with RLP.

Intravitreal Injection of Anti-vascular Endothelial Growth Factor Agents for Ocular Vascular Diseases: Clinical Practice Guideline.

PURPOSE: To provide the clinical recommendations for the administration of intravitreal anti-vascular endothelial growth factor (VEGF) drugs especially bavacizumab for ocular vascular diseases including diabetic macular edema, neovascular age-related macular degeneration, myopic choroidal neovascularization, retinal vein occlusion and central serous chorioretinopathy. METHODS: Twenty clinical questions were developed by the guideline technical committee. Relevant websites and databases were searched to find out the pertinent clinical practice guidelines to answer the questions. The technical committee provided possible answers (scenarios) according to the available evidences for each question. All scenarios along with their levels of evidence and the supported articles were sent to the experts for external review. If the experts did not agree on any of the scenarios for one particular clinical question, the technical committee reviewed all scenarios and their pertinent evidences and made the necessary decision. After that, the experts were asked to score them again. All confirmed scenarios were gathered as the final recommendations. RESULTS: All the experts agreed on at least one of the scenarios. The technical committee extracted the agreed scenario for each clinical question as the final recommendation. Finally, 56 recommendations were developed for the procedure of intravitreal anti-VEGF injection and their applications in the management of ocular vascular diseases. CONCLUSION: The implementation of this guideline can standardize the management of the common ocular vascular diseases by intravitreal injection of anti-VEGF agents. It can lead to better policy-making and evidence-based clinical decision by ophthalmologists and optimal evidence based eye care for patients.

Single-session photodynamic therapy combined with intravitreal bevacizumab and triamcinolone for neovascular age-related macular degeneration.

BACKGROUND: To evaluate the efficacy of triple therapy consisting of single-session photodynamic therapy (PDT), intravitreal bevacizumab (IVB) and intravitreal triamcinolone (IVT) as initial pulse therapy followed by repeat intravitreal bevacizumab injections for maintenance treatment in neovascular age-related macular degeneration (AMD). METHODS: In a prospective interventional case series, patients with subfoveal choroidal neovascularization (CNV) secondary to AMD underwent pulse therapy with single-session PDT according to the standard protocol followed by 1.25 mg IVB and 2 mg IVT 48 hours later. Best corrected visual acuity (BCVA) was assessed and optical coherence tomography (OCT) and fluorescein angiography (FA) were performed prior to treatment. BCVA and OCT measurements were repeated at 6 week intervals and FA was obtained after 12 weeks and when necessary thereafter. Repeat injections of IVB were performed based on fluorescein angiographic evidence of CNV leakage. RESULTS: This series included 17 eyes of 17 patients with mean age of 67.6 +/- 7.2 years. Mean follow up duration was 50.4 +/- 15.5 weeks. Mean BCVA prior to treatment was 0.74 +/- 0.33 logMAR which improved to 0.52 +/- 0.36 logMAR after 12 weeks (P = 0.012) and 0.41 +/- 0.38 logMAR after 24 weeks (P = 0.001). Mean pretreatment central macular thickness (CMT) was 395 +/- 181 micro which was significantly reduced to 217 +/- 69 micro (P = 0.005), 231 +/- 79 micro (P = 0.028) and 221 +/- 87 micro (P = 0.05) six, twelve and twenty-four weeks after initial treatment respectively. Visual acuity improvement and CMT reduction was maintained during the follow-up period. IVB injections were repeated once, twice and three times in 10, 7 and 2 eyes at a mean interval of 20.2 +/- 10.1, 19 +/- 13.7 and 15 +/- 1.4 weeks after initial therapy, respectively. CONCLUSION: Initial pulse triple therapy consisting of single-session PDT combined with IVB and IVT improves vision and reduces CMT in neovascular AMD. Repeat IVB injections maintain the visual gain from the initial combination therapy.