Three-year outcome of photodynamic therapy combined with VEGF inhibitor for pachychoroid neovasculopathy.

BACKGROUND: Long-term results of photodynamic therapy (PDT) combined with vascular endothelial growth factor (VEGF) inhibitors for pachychoroid neovasculopathy (PNV) are not yet clear. METHODS: This study is a retrospective, observational case series. We retrospectively examined untreated PNV cases (22 cases, 22 eyes, mean age of 71.0 years) who underwent PDT therapy in combination with VEGF inhibitors followed by additional treatments with pro re nata protocol. Visual acuity, number of treatments, and time to recurrence were examined. In addition, foveal choroidal thickness and choroidal vascularity index (CVI) were evaluated in 13 of 22 patients who were followed up with SpectralisOCTR from baseline. RESULTS: Fifteen (68%) cases had polyps at baseline. LogMAR visual acuity averaged 0.24 ± 0.20 (range, - 0.079 to 0.82) at baseline and significantly improved after 1, 2, and 3 years (p = 0. 004, 0.0003, 0.002, respectively). Fourteen patients (64%) recurred, with an average time to recurrence of 1.8 ± 0.9 years. Foveal choroidal thickness decreased significantly after 1 year (average from 326 µm to 263 µm) and remained unchanged up to 3 years (255 µm). CVI also decreased after 1 year (average from 0.62 to 0.61) and remained unchanged until 3 years later (0.60). CONCLUSIONS: We examined the 3-year course of PDT in combination with the VEGF inhibitor for untreated PNV. Visual acuity was improved, foveal choroidal thickness and CVI were decreased after 3 years.

Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes.

PURPOSE: To examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Comparing corneal biomechanic changes among solo cataract surgery, microhook ab interno trabeculotomy and iStent implantation.

Minimally invasive glaucoma surgery has expanded the surgical treatment options in glaucoma, particularly when combined with cataract surgery. It is clinically relevant to understand the associated postoperative changes in biomechanical properties because they are influential on the measurement of intraocular pressure (IOP) and play an important role in the pathogenesis of open-angle glaucoma (OAG). This retrospective case-control study included OAG patients who underwent cataract surgery combined with microhook ab interno trabeculotomy (µLOT group: 53 eyes of 36 patients) or iStent implantation (iStent group: 59 eyes of 37 patients) and 62 eyes of 42 solo cataract patients without glaucoma as a control group. Changes in ten biomechanical parameters measured with the Ocular Response Analyzer and Corneal Visualization Scheimpflug Technology (Corvis ST) at 3 and 6 months postoperatively relative to baseline were compared among the 3 groups. In all the groups, IOP significantly decreased postoperatively. In the µLOT and control groups, significant changes in Corvis ST-related parameters, including stiffness parameter A1 and stress‒strain index, indicated that the cornea became softer postoperatively. In contrast, these parameters were unchanged in the iStent group. Apart from IOP reduction, the results show variations in corneal biomechanical changes from minimally invasive glaucoma surgery combined with cataract surgery.

Immunogammopathy Maculopathy Secondary to Waldenström's Macroglobulinemia Complicated With Diabetic Retinopathy: A Case Report and Literature Review.

In Waldenström's Macroglobulinemia (WM), increased immunoglobulin M causes various signs and symptoms. It sometimes presents with macular edema. A 65-year-old WM patient with a five-year history of diabetes mellitus was evaluated for ocular complications. Fundus examination and optical coherence tomography showed retinal changes consistent with non-proliferative diabetic retinopathy and foveal detachment with intraretinal cysts in the right eye, suggesting diabetic macular edema. However, on fluorescein angiography, there was no leakage over the area of foveal detachment, which led to the diagnosis of immunogammopathy maculopathy secondary to WM for macular edema and foveal detachment. The patient's ocular manifestation remained unchanged through a follow-up period of 11 months without therapeutic interventions. Immunogammopathy maculopathy, a rare ocular manifestation of monoclonal gammopathy, demands differentiation from other causes of macular edema in WM patients. The present case highlights the importance of fluorescein angiography, or silent macula, in diabetic patients to distinguish immunogammopathy maculopathy from diabetic macular edema.

Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration.

PURPOSE: To identify the inflammatory cytokine profile in the aqueous humor (AH) of patients with intraocular inflammation (IOI) after intravitreal administration of brolucizumab (IVBr) for neovascular age-related macular degeneration. METHODS: Eight eyes from seven patients with IOI after initial IVBr (IVBrIOI +) were enrolled. Sixteen eyes from 16 patients without IOI after IVBr (IVBrIOI -) and aflibercept (IVA) were used as controls. AH samples were analyzed using a multiplex immunoassay. RESULTS: C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)1, CXCL10, CXCL13, interleukin (IL)-6, IL-8, IL-10, matrix metalloproteinase (MMP)-1, MMP-9, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), intercellular adhesion molecule (ICAM)-1, E-selectin, and P-selectin levels were significantly higher in IVBrIOI + than in IVBrIOI - and IVA. Vascular endothelial growth factor (VEGF) was significantly lower in IVBrIOI - compared to that in IVBrIOI + and IVA. In the IVBrIOI + group, there were significant correlations between CCL2, CXCL1, IL-6, IL-8, IL-10, G-CSF, GM-CSF, ICAM-1, and E-selectin, which also exhibited significant correlations in the IVBrIOI - group. CONCLUSION: The number of inflammatory cytokines increases during IOI, which is associated with type IV hypersensitivity and vascular inflammation. Some cytokines exhibit correlations even in non-inflamed eyes, indicating a subclinical response to IVBr.

The Association Between Age and Systemic Variables and the Longitudinal Trend of Intraocular Pressure in a Large-Scale Health Examination Cohort.

Purpose: The detailed effects of age and systemic factors on intraocular pressure (IOP) have not been fully understood because of the lack of a large-scale longitudinal investigation. This study aimed to investigate the effect of various systemic factors on the longitudinal change of IOP. Methods: There were a total of 20,909 eyes of 10,471 subjects from a health checkup cohort that were followed up for systemic factors: (i) age at baseline, (ii) sex, (iii) time series body mass index (BMI), (iv) time series smoking habits, (v) time series systolic and diastolic blood pressures (SBP and DBP), and (vi) time series 19 blood examinations (all of the time series data was acquired at each annual visit), along with IOP annually for at least 8 years. Then the longitudinal effect of the systemic factors on the change of IOP was investigated. Results: IOP significantly decreased by -0.084 mm Hg/year. BMI, SBP, DBP, smoking habits, total triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and glycosylated hemoglobin A1c were not significantly associated with the change of IOP. Higher values of age, aspartate aminotransferase, hemoglobin, platelet, and calcium were suggested to be significantly associated with the decrease of IOP, whereas higher alanine aminotransferase, guanosine triphosphate, white blood cell count, red blood cell count, and female gender were significantly associated with the increase of IOP. Conclusions: Age, aspartate aminotransferase, hemoglobin, platelet, calcium, alanine aminotransferase, guanosine triphosphate, white blood cell count, red blood cell count, and gender were the systemic variables significantly associated with the change of IOP.

RESTORATION PROCESS OF THE OUTER RETINAL LAYERS AFTER SURGICAL MACULAR HOLE CLOSURE.

PURPOSE: To investigate the interrelationship among the outer retinal layers after macular hole surgery and elucidate the restoration process. METHODS: This retrospective observational study included 50 eyes of 47 consecutive patients with closed macular holes in the first vitrectomy. Optical coherence tomography was obtained before surgery; at 1, 3, and 6 months postsurgery; and at the last visit. The complete continuous layer rate and mean defect length were evaluated for the outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ). RESULTS: At all postoperative visits, the complete continuous layer rate was in the descending order of ELM, ONL, and EZ and the mean defect length was in the ascending order of ELM, ONL, and EZ. External limiting membrane was necessary for ONL restoration. External limiting membrane and ONL were necessary for EZ restoration. Hyperreflective protrusions were observed from the area lacking ELM into the subretinal space after surgery. Ellipsoid zone was not formed in coexistence with the hyperreflective protrusions. Intermediate reflective protrusions appeared under the ONL plus ELM after surgery and were eventually replaced by EZ. CONCLUSION: Restoration of the outer retinal layers after surgical macular hole closure occurs in the order of ELM, ONL, and EZ.

Comparative analysis of polypoidal choroidal vasculopathy with and without hemorrhage treated by anti-VEGF monotherapy.

PURPOSE: Visual function and treatment response after anti-vascular endothelial growth factor monotherapy were compared between polypoidal choroidal vasculopathy (PCV) with and without hemorrhage. METHODS: We conducted a retrospective, observational study (mean, 26 months) for 49 eyes of 49 treatment-naive patients with PCV. Patients were classified into PCV with hemorrhage (26 eyes) or without hemorrhage (23 eyes). PCV with massive hemorrhage subgroup has four or more disc-hemorrhagic areas and included five eyes. RESULTS: There were no significant differences in patient age, sex, systolic blood pressure, diastolic blood pressure, presence of choroidal vascular hyperpermeability, number of polyps, maximum polyp size, lesion area, and presence of pigment epithelium detachment (PED) between the two groups. Except for the course of PCV-related hemorrhage, treatment number and its response were similar between the groups. Best-corrected visual acuity at the last visit in PCV with hemorrhage was 0.33 ± 0.51 logMAR (20/41) comparable with 0.28 ± 0.41 logMAR (20/38) without hemorrhage at the last visit (p = 0.944). Maximum polyp size in massive hemorrhagic PCV was significantly larger (314.6 ± 111.4 µm) than that of small hemorrhagic PCV (229.0 ± 119.1 µm; p = 0.037). All PCV with massive hemorrhage was accompanied by large hemorrhagic PED. CONCLUSION: There were no significant differences in the baseline characteristics, treatment intervention, or suppression of disease activity between PCV with and without hemorrhage. Final visual acuity of PCV did not differ with or without hemorrhage. Development of massive hemorrhaging in PCV may be associated with both large polyps and hemorrhagic PED.

The usefulness of the retinal sensitivity measurement with a microperimetry for predicting the visual prognosis of branch retinal vein occlusion with macular edema.

PURPOSE: To evaluate the usefulness of the retinal sensitivity in branch retinal vein occlusion (BVO) with macular edema (ME) following the anti-vascular endothelial growth factor (anti-VEGF) treatment. METHODS: Best-corrected visual acuity (BCVA), microperimetry, and optical coherence tomography (OCT) measurements were carried out in 20 patients with BVO with ME, at baseline and 1 month after the anti-VEGF treatment. The relationships among BCVA, mean retinal sensitivity (MS), macular volume (MV), central retinal thickness (CRT), integrity of ellipsoid zone (EZ), mean retinal sensitivity in the most affected quadrant (qMS), and macular volume in the most affected quadrant (qMV) were investigated. In addition, the relationships among the change in BCVA at 1 month (ΔBCVA1m), mean sensitivity in the most affected quadrant at 1 month (ΔqMS1m), MV in the most affected quadrant at 1 month (ΔqMV1m), and CRT at 1 month (ΔCRT1m) were analyzed. The optimal model for BCVA at 3 months after the treatment (BCVA3m) was identified. RESULTS: There was not a significant difference in BCVA (paired Wilcoxon test, p = 0.058) between at baseline and after the treatment, but there were significant differences in MS, MV, CRT, qMS, and qMV (p < 0.05). There was a significant relationship between ΔqMS1m and ΔMV1m, ΔCRT1m, and ΔqMV1m, respectively. ΔMS1m or ΔqMS1m and BCVA at baseline and ΔBCVA1m were selected as explanatory variables in the optimal model for BCVA3m. CONCLUSION: Retinal sensitivity was related to retinal structure, whereas this was not the case with BCVA. In addition, retinal sensitivity was useful to predict BCVA after anti-VEGF therapy.

The effect of air pulse-driven whole eye motion on the association between corneal hysteresis and glaucomatous visual field progression.

Corneal hysteresis (CH) measured with Ocular Response Analyzer (Reichert: ORA) has been reported to be closely related to the glaucomatous visual field (VF) progression. The air pulse applied to an eye not only induces corneal deformation, but also whole eye motion (WEM), which may result in an inaccurate measurement of CH. Here we investigated the influence of air pulse-driven WEM measured with the Corivs ST (CST®, OCULUS) on the relationship between CH and VF progression in primary open angle-glaucoma patients. Using the CST parameters of the maximal WEM displacement (WEM-d) and the time to reach that displacement (WEM-t), the eyes were classified into subgroups (WEM-d low- and high-group, and WEM-t short- and long-group). For the whole population and all subgroups, the optimal linear mixed model to describe mean of total deviation (mTD) progression rate with eight reliable VFs was selected from all combinations of seven parameters including CH. As a result, optimal models for the mTD progression rate included CH in the whole population, the WEM-d low- group and the WEM-t short-group, but not in the WEM-d high-group and the WEM-t long-group. Our findings indicated association between CH and glaucomatous progression can be weakened because of large WEM.