Ziv-aflibercept in Diabetic Macular Edema: Relation of Subfoveal Choroidal Thickness with Visual and Anatomical Outcomes.

Purpose: To evaluate the effects of intravitreal ziv-aflibercept injections (IVZ) on subfoveal choroidal thickness (SCT) as well as on central macular thickness (CMT) and on best corrected visual acuity (BCVA) changes in eyes with center-involved diabetic macular edema (CI-DME). Methods: Fifty-seven eyes of 36 patients with CI-DME were included in this prospective interventional case series. Structural optical coherence tomography (OCT) and enhanced depth imaging OCT were performed at baseline followed by three monthly 1.25 mg IVZ injections. Changes of SCT, CMT, and BCVA at each follow-up session were assessed. The association between baseline SCT and its monthly changes with final visual and anatomical outcomes were also assessed. Results: CMT at baseline, and at the first, second, and third month follow-up sessions were 396 ± 119, 344 ± 115, 305 ± 89, and 296 ± 101 µm, respectively (P-value < 0.001). SCT at baseline, and at months one, two, and three were 236 ± 47, 245 ± 56, 254 ± 54, and 241 ± 54 µm, respectively (P-value > 0.99). Corresponding figures for BCVA were 0.58 ± 0.29, 0.47 ± 0.31, 0.4 ± 0.24, and 0.37 ± 0.23 LogMAR, respectively (P-value < 0.001). There was a statistically significant positive correlation between BCVA and CMT changes following IVZ injections (P-value < 0.001). However, there were no significant correlations between SCT changes and visual acuity (VA) and CMT changes following IVZ injections. Conclusion: IVZ improved visual outcomes and macular thickness profiles in patients with CI-DME. However, IVZ had no significant effect on SCT. Baseline SCT and its monthly changes had no association with visual and anatomical outcomes.

Multimodal imaging in pachychoroid spectrum.

Diagnostic investigation on pachychoroid spectrum disease (PSD) has been growing along with the rapid advancement of imaging technology. In optical coherence tomography (OCT)-based studies, choroidal thickness profile, luminal and stromal choroidal ratio, and abnormalities in the neurosensory retina have demonstrated various patterns in different clinical entities related to PSD. The emerging role of OCT angiography ()CTA) has been expanded to involve the quantitative analysis of the OCTA parameters in different clinical entities of PSD and to evaluate the choriocapillaris signal void and vessel density as indicators of choriocapillaris ischemia. OCTA has broadened our knowledge in characterization and assessment of both active and quiescent choroidal neovascularization and its association with treatment response. Recent studies using indocyanine green angiography have focused on the evaluation of choroidal vascular hyperpermeability and its relationship with other pachychoroid related features. Ultra-widefield indocyanine green angiography enables observation and characterization of peripheral choroidal pathologies and their associations with macular abnormalities. Multicolor imaging is an emerging modality with the capability to demonstrate early abnormalities in PSD. We summarize all investigations reflecting the new insights into the application of multimodal imaging for PSD and focus on novel findings observed in different clinical entities with each imaging modality.

Retinal Vascular Response to Hyperoxia in Patients with Diabetes Mellitus without Diabetic Retinopathy.

PURPOSE: To evaluate the retinal vascular response to hyperoxia in patients with diabetes at the preclinical stage of diabetic retinopathy (DR) and to quantify the changes in comparison with normal subjects using optical coherence tomography angiography (OCTA). METHODS: In this prospective study, 40 eyes of 20 participants comprising 10 diabetic patients with no diabetic retinopathy (NDR) and 10 normal subjects were recruited. OCTA images were acquired in the resting position and were repeated after a hyperoxic challenge using a nasal mask connected to a reservoir bag supplying 100% oxygen at the rate of 15 L per minute for 5 minutes. The changes of mean parafoveal vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the foveal avascular zone (FAZ) size, and the outer retina flow index were compared between two conditions in each group and between the two study groups. The statistical significance of differences in the means was evaluated using Student's t-test for unpaired samples with consideration of the generalized estimating equations (GEE) for intereye correlation. RESULTS: At baseline, the mean parafoveal VD of SCP and DCP were significantly lower in the NDR participants compared to the healthy subjects (P < 0.001 and P = 0.006, respectively). After induction of the hyperoxic challenge in healthy participants, mean parafoveal VD reduced at both the SCP and DCP, but reached a statistical significance only in DCP (P = 0.006). However, following induction of hyperoxic challenge in patients with NDR, no significant decline was noticed in mean parafoveal VD of SCP and DCP. The degree of change in mean parafoveal VD of DCP was statistically significantly more pronounced in healthy subjects compared to the NDR group (P = 0.034). The change in FAZ size and the outer retina flow index were comparable between the two study groups. CONCLUSION: Retinal capillary layers responded differently to hyperoxia-induced challenge, and in normal subjects, the autoregulatory mechanism was mostly effective in the parafoveal DCP. Retinal vascular reactivity was impaired in SCP and DCP at the preclinical stage of DR. OCTA as a noninvasive modality was able to quantify the retinal vascular response to the hyperoxic challenge.

Quantitative analysis of optical coherence tomography angiography metrics in diabetic retinopathy.

PURPOSE: To evaluate the correlation of the visual acuity and diabetic retinopathy stage using optical coherence tomography and optical coherence tomography angiography metrics. METHODS: In this prospective study, optical coherence tomography and optical coherence tomography angiography images of patients with different stages of diabetic retinopathy were obtained. In optical coherence tomography angiography images, the size of foveal avascular zone, central macular thickness, and vessel density at superficial and deep capillary layers of the macula were measured. In optical coherence tomography images, the presence of intraretinal cyst, disorganization of retinal inner layer, and ellipsoid zone and external limiting membrane disruption were evaluated. The associations between the variables with visual acuity and diabetic retinopathy stage were analyzed. RESULTS: In total, 68 eyes of 38 patients with a mean age of 58.96 ± 10.59 years were included. In total, 34 eyes were categorized as non-proliferative diabetic retinopathy, 14 as active, and 20 as regressed proliferative diabetic retinopathy. Univariate analysis showed deep parafoveal vessel density, central macular thickness, ellipsoid zone disruption, disorganization of retinal inner layer, and external limiting membrane disruption had a significant relationship with visual acuity. However, in multivariate analysis, only central macular thickness and ellipsoid zone disruption had significant association with visual acuity (p = 0.02 and p = 0.01, respectively). There was a significant difference in deep parafoveal vessel density (p = 0.04), but not in foveal avascular zone area, between different stages of diabetic retinopathy. CONCLUSION: In this study, the foveal avascular zone area did not correlate with visual acuity and different stages of diabetic retinopathy. Structural abnormalities on optical coherence tomography images with especial focus on outer retinal disruption provided more reliable predictors for visual acuity outcomes in patients with diabetic retinopathy.

The effect of acute warming and thermal acclimation on maximum heart rate of the common killifish Fundulus heteroclitus.

Common killifish Fundulus heteroclitus were acclimated to ecologically relevant temperatures (5, 15 and 33°C) and their maximum heart rate (fHmax ) was measured at each acclimation temperature during an acute warming protocol. Acclimation to 33°C increased peak fHmax by up to 32% and allowed the heart to beat rhythmically at a temperature 10°C higher when compared with acclimation to 5°C. Independent of acclimation temperature, peak fHmax occurred about 3°C cooler than the temperature that first produced cardiac arrhythmias. Thus, when compared with previously published values for the critical thermal maximum of F. heteroclitus, the temperature for peak fHmax was cooler and the temperature that first produced cardiac arrhythmias was similar to these critical thermal maxima. The considerable thermal plasticity of fHmax demonstrated in the present study is entirely consistent with eurythermal ecology of killifish, as shown previously for another eurythermal fish Gillichthys mirabilis.

Autologous Platelet-rich Plasma Eye Drops Accelerate Re-epithelialization of Post-keratoplasty Persistent Corneal Epithelial Defects.

PURPOSE: To investigate whether autologous platelet-rich plasma (PRP) eye drops accelerate re-epithelialization of post-keratoplasty persistent corneal epithelial defects (PEDs). METHODS: A total of 34 eyes with PEDs after keratoplasty (24 penetrating keratoplasty and 10 deep anterior lamellar keratoplasty) that were refractory to conventional medical treatments were treated with PRP eye drops every 3 hours. PRP eye drops were prepared with a low- and high-speed centrifugation method and final platelet counts were 700,000-800,000 plt/µl. The mean treatment duration for complete re-epithelialization was compared with the mean treatment duration of conventionally treated corneal defects before the PRP treatment by paired t-test. The mean treatment duration was also statistically analyzed between age groups, gender, indications for keratoplasty, and types of keratoplasty using analysis of variance (ANOVA). RESULTS: Treatment with autologous PRP eye drops led to rapid re-epithelialization in all eyes. The mean treatment duration for complete re-epithelialization was 2.47 ± 1.21 weeks, which was significantly shorter than the mean treatment duration of conventionally treated corneal defects before PRP treatment (6.82 ± 1.24 weeks) (P = 0.0001). There was no significant correlation between re-epithelialization time and patients' age, sex, indications for keratoplasty, and techniques of corneal transplantation. CONCLUSION: Treatment with autologous PRP eye drops is an effective and reliable approach that accelerates re-epithelialization of post-transplantation PEDs.

Early detection of diabetic retinopathy.

Diabetic retinopathy (DR) is a primary cause of visual impairment worldwide. Diabetes mellitus may be associated with ophthalmoscopically nonvisible neurovascular damage that progresses before the first clinical signs of DR appear. Reduction of the inner neuroretinal layer thickness on macular optical coherence tomography, reduced contrast sensitivity primarily at low spatial frequencies, abnormal results in color vision and microperimetry tests, and a prolonged implicit time recorded by multifocal electroretinography have been proposed for detection of early functional and nonvisible structural neuroretinal changes. Vascular abnormalities such as changes in the retinal vessel caliber, architectural indices, and blood flow have been investigated to evaluate the early stages of DR. The results of optical coherence tomography angiography, retinal vessel oxygen saturation patterns, and elevated levels of circulating blood markers and cytokines have been suggested as early signs of DR. Light-based molecular imaging in rodents has been developed to demonstrate changes in protein expressions in the retinal microvessels as diagnostic biomarkers. Future clinical studies will examine the safety and efficacy of this approach in humans. We summarize all the studies related to subclinical DR biomarkers.

Contrast sensitivity to spatial gratings in moderate and dim light conditions in patients with diabetes in the absence of diabetic retinopathy.

OBJECTIVE: To evaluate the ability of contrast sensitivity (CS) to discriminate loss of visual function in diabetic subjects with no clinical signs of retinopathy relative to that of normal subjects. RESEARCH DESIGN AND METHODS: In this prospective cross-sectional study, we measured CS in 46 diabetic subjects with a mean age of 48±6 years, a best-corrected visual acuity of 20/20 and no signs of diabetic retinopathy. The CS in these subjects was compared with CS measurements in 46 normal control subjects at four spatial frequencies (3, 6, 12, 18 cycles per degree) under moderate (500 lux) and dim (less than 2 lux) background light conditions. RESULTS: CS was approximately 0.16 log units lower in patients with diabetes relative to controls both in moderate and in dim background light conditions. Logistic regression classification and receiver operating characteristic curve analysis indicated that CS analysis using two light conditions was more accurate (0.78) overall compared with CS analysis using only a single illumination condition (accuracy values were 0.67 and 0.70 in moderate and dim light conditions, respectively). CONCLUSIONS: Our results showed that patients with diabetes without clinical signs of retinopathy exhibit a uniform loss in CS at all spatial frequencies tested. Measuring the loss in CS at two spatial frequencies (3 and 6 cycles per degree) and two light conditions (moderate and dim) is sufficiently robust to classify diabetic subjects with no retinopathy versus control subjects.

Correlations Between Histopathologic Changes and Clinical Features in Pterygia.

PURPOSE: To investigate the correlations between clinical findings and histopathologic changes in eyes with pterygium. METHODS: This prospective study included 70 eyes with primary pterygia undergoing surgical excision. Prior to surgery, clinical features of the pterygia including extension over the cornea, redness, fleshiness (based on obscuration of the underlying episcleral vessels), and obliteration of the plica semilunaris were determined. Postoperatively, pterygium specimens were examined by hematoxylin-eosin and trichrome staining to evaluate histopathologic characteristics including vascular density, leukocytic infiltration, stromal elastosis, stromal fibrosis and subepithelial fibrosis. Correlations between clinical findings and histopathologic changes were then investigated. RESULTS: There was a marginally significant correlation between the redness and the fleshiness of pterygium (P = 0.06). Both redness and fleshiness of the pterygium had significant positive correlation with dimensions of the lesion over the cornea. Moreover, larger pterygia were associated with obliteration of the plica semilunaris. Pterygium redness showed a significant correlation with vascular density (P = 0.04), and pterygium fleshiness had a significant correlation with stromal fibrosis (P = 0.04). Pterygium dimensions over the cornea demonstrated a positive correlation with vascular density and a negative correlation with stromal elastosis. CONCLUSION: Redness and fleshiness of pterygium were only marginally correlated with each other, and each one showed a correlation with different histopathologic features. Larger pterygia were associated with more significant changes at the clinical and histopathologic levels.

Macular thickness measurement in clinically significant macular edema before and after meal.

PURPOSE: To evaluate the macular thickness changes in diabetic macular edema after meal. METHODS: In this prospective case series, macular thicknesses of diabetic patients with clinically significant macular edema (CSME) were measured after 7 h of fasting and repeated 2 h after breakfast. RESULTS: Thirty six eyes of 20 diabetic patients were evaluated. The mean central subfield thickness (CST) and maximum retinal thickness (MRT) significantly decreased after meal (mean change of -10.3 ± 14.3 µm and -13.1 ± 12.7 µm, respectively, both P < 0.001). A decrease in CST and MRT values was found in 23 (63.8%) and 28 (77.7%) eyes, respectively, and no eye had an increase in retinal thickness measurements. Significant correlation was found between CST and MRT change and fasting thickness measurements (P = 0.001 and P = 0.01, respectively) and intraretinal cystic spaces (P = 0.001 and P = 0.03, respectively). Mean MRT change was significantly higher in the presence of subretinal fluid (P = 0.01). CONCLUSION: Retinal thickness measurements may change after meal. So, fasting state of diabetic patient should be considered in measurement of macular thickness of patients with CSME.

Effect of grid decentration on macular thickness measurements in normal subjects and patients with diabetic macular edema.

PURPOSE: To evaluate the effect of optical coherence tomography (OCT) grid decentration on macular thickness measurements in healthy subjects and patients with diabetic macular edema. METHODS: In this prospective study, 3D spectral-domain OCT images of 51 eyes with clinically significant diabetic macular edema and 29 healthy eyes were assessed. In each eye, the macular Early Treatment Diabetic Retinopathy Study grid was evaluated for decentration. After grid adjustment, changes in central subfield thickness (CST) and central subfield volume (CSV) measurements were recorded. Changes >1 µm and >8.5 µm in CST were considered as grid decentration and clinically significant grid decentration, respectively. RESULTS: Grid decentration was found in 10 normal eyes (34.6%) and 32 clinically significant macular edema (CSME) eyes (62.7%, p = 0.01). Clinically significant CST changes were found in 3 normal eyes (10.3%) and 23 CSME eyes (45%, p = 0.001). The mean change in CST after grid adjustment was 6.4 ± 5.8 µm and 24.7 ± 27 µm in normal and CSME eyes (p = 0.04). Age, sex, and CST had no statistically significant effect on grid decentration in normal and CSME eyes. Best-corrected visual acuity was significantly worse in eyes with grid decentration (0.75 ± 0.55 vs 0.42 ± 0.22 logMAR, p = 0.02) and clinically significant grid decentration (0.81 ± 0.6 vs 0.45 ± 0.27 logMAR, p = 0.01). Change in CSV was detected in 3 normal eyes (10.3%) and 24 CSME eyes (47%, p = 0.001). CONCLUSIONS: Grid decentration occurs in a large number of OCT thickness maps and leads to significant error in macular thickness measurements. The effect is more prominent in patients with CSME.

Effects of pterygium surgery on front and back corneal astigmatism.

OBJECTIVE: To evaluate changes in front and back corneal astigmatism after pterygium surgery using the Scheimpflug imaging of Pentacam. DESIGN: Prospective interventional case series. PARTICIPANTS: We studied 96 eyes with primary pterygium that underwent surgery. METHODS: Preoperatively and at 1, 3, and 6 months after surgery, Pentacam (Oculus, Wetzlar, Germany) was used to measure astigmatism at the front and back corneal surfaces. Surgically induced astigmatism (SIA) on the front corneal surface was also calculated, using vector analysis. RESULTS: Of the eyes, 73 completed 6-month postoperative follow-up without developing pterygium recurrence. Front corneal astigmatism decreased from 3.97 ± 4.49 D preoperatively to 1.23 ± 1.88 D at 1 month (p < 0.001). Back corneal astigmatism decreased, but nonsignificantly, from 0.35 ± 0.39 D preoperatively to 0.32 ± 0.2 D at 1 month (p = 0.49). However, although back astigmatism was with-the-rule in 43.8% of patients and against-the-rule in 24.6% of patients preoperatively, these changed to 87.7% and 4.1%, respectively, at 1 month (p = 0.02). Refractive cylinder (52 eyes) reduced from 2.62 ± 2.22 D preoperatively to 1.06 ± 1.57 D at 1 month (p = 0.05). There was no significant change in any parameter after 1 month throughout the 6 months after surgery. SIA was 3.51 ± 2.66 D at 1 month postoperatively, which showed significant correlation with age, preoperative astigmatism, and pterygium length and area, but there was no correlation with gender, pterygium width, preoperative spherical power, or surgical technique. Moreover, higher grades of pterygium morphology had higher SIA postoperatively (p = 0.05). CONCLUSIONS: Pterygium surgery was associated with significant changes in front and back corneal surfaces. Eyes with more advanced pterygia achieved higher SIA.

Effects of pterygium surgery on front and back corneal surfaces and anterior segment parameters.

The purpose of this study was to evaluate the effects of pterygium surgery on front and back corneal surfaces and anterior segment parameters. This prospective study included 96 eyes with primary pterygium that underwent surgery. Preoperatively and at 1, 3, and 6 months postoperatively, Pentacam was used to evaluate front and back corneal surfaces, anterior chamber depth (ACD), anterior chamber angle (ACA) and anterior chamber volume (ACV). Mean simulated keratometry at the front corneal surface increased from 42.73 ± 2.21 D preoperatively to 44.45 ± 2.05 D at 1 month (P < 0.001); it then decreased to 44.32 ± 2.07 D at 3 months (P < 0.001) and 44.19 ± 2.10 D at 6 months (P = 0.01). There was no statistically significant change in mean simulated keratometry at the back corneal surface. Radius of the front corneal best-fit sphere (BFS) decreased from 7.99 ± 0.29 mm preoperatively to 7.77 ± 0.25 mm at 1 month postoperatively (P < 0.001), without further change up to 6 months. Radius of the back corneal BFS increased from 6.42 ± 0.24 mm preoperatively to 6.50 ± 0.24 mm at 1 month (P < 0.001), without further change. Postoperative changes in mean simulated keratometry and radii of BFS had statistically significant positive correlations with pterygium extension onto the cornea and grade of pterygium morphology but, not with the surgical technique. There were no significant changes in ACD, ACA, and ACV values after pterygium surgery. Furthermore, the spherical equivalent of manifest refraction changed from +0.75 ± 1.06 D preoperatively to -0.72 ± 1.33 D at 1 month postoperatively (P = 0.001), with no further significant change. In conclusion, after pterygium surgery there were significant changes in front mean keratometry and front and back corneal radii of BFS. These were correlated with preoperative pterygium size and morphology grade. No significant changes in anterior segment parameters were noted postoperatively.

Visual outcome and contrast sensitivity after photorefractive keratectomy in low to moderate myopia: wavefront-optimized versus conventional methods.

PURPOSE: To compare visual outcomes and contrast sensitivity after wavefront-optimized or conventional photorefractive keratectomy (PRK) in myopic patients with or without astigmatism. SETTING: Vanak Eye Surgery Center, Tehran, Iran. DESIGN: Comparative case series. METHODS: Patients with low to moderate myopia with or without astigmatism were allocated into 2 groups. The study group was treated with wavefront-optimized PRK (Allegretto Wave Eye-Q software version 2.020 default treatment) and the control group, with conventional PRK (Technolas 217z). In all cases, treatments were bilateral and performed with the same device. Baseline and 3-month postoperative measures were uncorrected and corrected distance visual acuities, manifest refraction, and contrast sensitivity. RESULTS: Each group comprised 66 eyes. The mean preoperative spherical equivalent refraction improved from -2.99 diopters (D) ± 1.02 (SD) preoperatively to -0.08 ± 0.26 D 3 months postoperatively in the study group and from -2.66 ± 0.95 D to 0.01 ± 0.30 D, respectively, in the control group. In both groups, the postoperative mesopic and photopic contrast sensitivity decreased significantly at most spatial frequencies. The postoperative decrease in contrast sensitivity in both groups was comparable except at spatial frequencies of 3 cycles per degree (cpd) under mesopic conditions and 12 cpd under photopic conditions, frequencies at which the control group had a greater reduction. CONCLUSIONS: Visual acuity and refractive error outcomes were similar in both treatment groups. After 3 months, mesopic and photopic contrast sensitivity were significantly decreased in both groups; the reduction in the 2 groups was almost comparable. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.