A Case of Osteopetrosis with Orbital Inflammation Secondary to Maxillary Osteomyelitis.

Introduction: Osteopetrosis is a rare heritable disorder characterized by increased bone density resulting from osteoclast dysfunction. Major complications include bone fracture, osteomyelitis, anemia, and cranial nerve compression. Optic atrophy can occur due to compression of the optic nerve. Although osteomyelitis of the jaw is a common complication, it rarely occurs in the maxilla. Here, we report a case of a 74-year-old female with osteopetrosis who developed maxillary osteomyelitis, leading to orbital inflammation. Case Presentation: She was referred to our clinic for 2 months of ptosis and swelling of the left eyelid and temporal region. Previous imaging revealed a left intraorbital occupying lesion, but a biopsy of the temporal subcutaneous tissue did not provide a definitive diagnosis. After 7 months, she presented with severe temporal swelling and purulent discharge. Upon examination, maxillary osteomyelitis resulting from caries of the upper jaw was observed. Treatment with oral antibiotics, drainage of the temporal skin fistula, and regular cleaning of the maxillary drainage improved her symptoms. Conclusion: This is a rare case of maxillary osteomyelitis associated with osteopetrosis, causing orbital inflammation.

Incidence and prognosis of taxane-induced macular edema: a retrospective study from the Japan Clinical REtina Study Group (J-CREST).

Macular edema is a known side effect of taxane-based anticancer drugs. We retrospectively investigated data from 11 centers between January 2016 and December 2021. Among 14,260 patients, 30 (0.21%) developed macular edema; from these, the number of cases associated with nab-paclitaxel was 16 (0.43%), significantly higher than the number of cases associated with paclitaxel or docetaxel (P < 0.01). Visual acuity (VA) and retinal choroidal change were examined in 27 patients, with a follow-up of at least 3 months. The patients' mean age was 67.2 years; 14 (51.3%) were male and four (14.8%) had unilateral onset. The mean interval between anticancer drug initiation and the first ophthalmology visit was 290.1 days. Among the 20 patients who discontinued anticancer drugs, VA and edema significantly improved 2 months after discontinuation (LogMAR VA: 0.50 vs. 0.28, central retinal thickness: 472.7 µm vs. 282.5 µm, both P < 0.01). No significant changes were observed in the central choroidal thickness. A correlation was found between duration of taxane treatment and VA immediately before discontinuation of anticancer drugs (ß = 0.00050; 95% confidence interval: 0.00036-0.00097; P < 0.05). Although taxane-induced macular edema is reversible, slower anticancer drug discontinuation worsened VA, highlighting the need for regular ophthalmologic evaluation during treatments.

Characterization of the visually impaired patients with diabetes mellitus in Japan.

AIMS/INTRODUCTION: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. MATERIALS AND METHODS: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. RESULTS: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively. CONCLUSIONS: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.

Ocular expression of cyclin-dependent kinase 5 in patients with proliferative diabetic retinopathy.

AIMS/INTRODUCTION: Inhibition of peroxisome proliferator-activated receptor gamma (PPARγ) phosphorylation mediated by cyclin-dependent kinase 5 (Cdk5) is one of the main mechanisms of action of antidiabetic drugs. In this study, we analyzed the ocular expression and activation of Cdk5 in patients with proliferative diabetic retinopathy (PDR). MATERIALS AND METHODS: The concentrations of PPARγ, Cdk5 and its activating subunit (p35) were determined in the vitreous body of 24 PDR and 63 control eyes by enzyme-linked immunosorbent assay. In addition, the messenger ribonucleic acid and protein expression levels of PPARγ, Cdk5 and p35 were measured in proliferative neovascular membranes from seven PDR eyes and non-neovascular epiretinal membranes from five control eyes by quantitative real-time polymerase chain reaction and immunohistochemical analysis. RESULTS: PPARγ, Cdk5 and p35 concentrations in the vitreous body were significantly higher in the PDR group compared with the control group. There was also a positive significant correlation of Cdk5 with PPARγ and p35 in the PDR group. Furthermore, the messenger ribonucleic acid expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes were significantly higher in the PDR group compared with the control group. Immunostaining showed increased protein expression levels of PPARγ, Cdk5 and p35 in proliferative neovascular membranes in the PDR group compared with the control group. CONCLUSIONS: Cdk5 activation is involved in PDR pathogenesis through PPARγ expression, and inhibition of Cdk5-mediated PPARγ phosphorylation might be a new therapeutic target for treatment of PDR.

A Case of Vogt-Koyanagi-Harada Disease-Like Uveitis Induced by Nivolumab and Ipilimumab Combination Therapy.

Nivolumab and ipilimumab are widely used immune checkpoint inhibitors (ICPIs) for the treatment of metastatic melanoma. ICPIs cause an array of side effects called immune-related adverse events (IRAEs) due to activation of an immune response. ICPI-uveitis can cause irreversible vision loss if untreated. There are few reports of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis induced by nivolumab and ipilimumab. We report a case of VKH disease-like uveitis recurrence after resuming ICPIs. A 73-year-old man with advanced melanoma was referred to our clinic with visual loss 25 days after starting nivolumab/ipilimumab. His corrected visual acuity was 0.5 in the right eye and 0.02 in the left eye. Enhanced-depth imaging optical coherence tomography (EDI-OCT) showed marked choroid thickening. The patient was diagnosed with VKH disease-like uveitis due to IRAEs. Subtenon injection of triamcinolone acetonide was performed, and nivolumab/ipilimumab was suspended, but serous retinal detachment (SRD) markedly worsened and choroidal detachment appeared. With 2 courses of steroid pulse therapy and oral steroids, SRD disappeared, and corrected visual acuity recovered in both eyes. Five months after the first injection, exacerbation of melanoma was observed, and nivolumab and oral steroids were restarted. Six weeks later, an increase in choroidal thickness was observed with EDI-OCT and diagnosed as a recurrence of VKH disease-like uveitis. Monitoring for the recurrence of VKH disease-like uveitis during the administration of ICPIs, even after uveitis is treated, is essential. Assessment of choroidal thickness with EDI-OCT may be useful for detecting early signs of VKH disease-like uveitis.

Changes in Choroidal Component Ratio and Circulation After Coffee Intake in Healthy Subjects.

Purpose: The effects of coffee intake on the ratio of stromal and luminal components in the choroid and the underlying mechanism remain unclear. This prospective cross-sectional study aimed to explore how coffee intake affects the choroidal component ratio and circulation. Methods: Forty-nine right eyes of healthy adult volunteers were evaluated as the coffee intake group. Thirty-two right eyes of healthy volunteers served as the control group. The participants consumed 185 mL of coffee or water, respectively, and the systemic hemodynamics, enhanced-depth imaging optical coherence tomographic (EDI-OCT) images, and foveal mean blur rate (MBR), an indicator of blood flow velocity, were recorded at baseline and after coffee or water intake. The EDI-OCT images were binarized using ImageJ software, and subfoveal choroidal thickness (SCT) and whole, luminal, and stromal choroidal areas were calculated. Results: In the coffee intake group, significant decreases in SCT and luminal area peaked at 60 minutes after intake (both P < 0.001), whereas a significant increase in MBR peaked at 30 minutes (P < 0.001). No significant stromal area fluctuations were observed. SCT and luminal area fluctuations exhibited a significant positive correlation (r = 0.978, P < 0.001). Significant negative correlations of luminal area fluctuations with MBR fluctuations were observed by stepwise regression analysis (r = -0.220, P < 0.001). The control group exhibited no significant fluctuations. Conclusions: Coffee-induced choroidal thinning may result mainly from a reduction in the choroidal vessel lumen, and this vessel lumen reduction correlated with an increased choroidal blood flow velocity after coffee intake. These coffee-induced changes in choroidal component ratio and circulation should be considered when evaluating choroids.

Changes in choroidal structure following intravitreal aflibercept therapy for retinal vein occlusion.

AIMS: To examine the choroidal change accompanying retinal vein occlusion (RVO) in detail, we measured changes in choroidal structure after intravitreal aflibercept (IVA) injections for RVO using binarisation of enhanced depth imaging optical coherence tomographic (EDI-OCT) images and assessed associations with clinical outcome. METHODS: Retrospective, observational case series. Forty treatment-naïve patients (10 central, 18 major branch and 12 macular branch RVO) were examined by EDI-OCT before and 1, 3 and 6 months after IVA injections. EDI-OCT images were binarised using ImageJ. Subfoveal cross-sectional areas of the luminal, stromal and total choroid over a 1500 µm span were measured and the stromal area to total choroidal area (S/C) ratio was calculated. RESULTS: Compared to normal contralateral eyes, afflicted eyes at baseline exhibited significantly greater stromal area (p<0.001), total choroidal area (p=0.001) and S/C ratio (p<0.001), but no difference in luminal area (p=0.083). The stromal area, S/C ratio and total choroidal area were significantly reduced in afflicted eyes at 1, 3 and 6 months after IVA (all p<0.006). Baseline S/C ratio was significantly correlated with baseline visual acuity (VA), baseline central retinal thickness (CRT) and VA and CRT improvement at 1, 3 and 6 months post-treatment even after adjusting for the axial length, age and sex (all p<0.012). CONCLUSION: RVO induces substantial oedema of the choroidal stromal area that is detectable by binarisation of EDI-OCT images. This stromal oedema likely stems from high intraocular vascular endothelial growth factor levels. Changes in choroidal structure may be used to assess severity and prognosis of RVO.

Suspected Gentamicin-Induced Retinal Vascular Occlusion after Vitrectomy.

Retinal vascular occlusion after ocular surgery is a rare but serious complication. A history of cardiovascular diseases, retrobulbar anesthesia injection, high intraocular pressure during the perioperative period, and drug toxicity have been reported as possible causative factors. We report here two cases of multiple retinal vascular occlusions after the subconjunctival injection of gentamicin at the end of uncomplicated 25-gauge vitrectomy. Case 1 was a 61-year-old man who developed a macular hole in the right eye. Phacovitrectomy with gas tamponade was performed. On postoperative day (POD) 1, dot hemorrhage was observed on the temporal side of the optic disk. On POD10, macular whitening, retinal hemorrhage, and multiple occlusion of retinal arteries and veins were observed. Case 2 was a 51-year-old woman who was diagnosed with rhegmatogenous retinal detachment in the right eye and underwent phacovitrectomy with gas tamponade. On POD3, macular whitening with cotton wool spots and retinal hemorrhage were observed with macular ischemia owing to occlusion of retinal arteries and veins. In both cases, subconjunctival injection of gentamicin given at the end of surgery was the most suspected cause of retinal vascular occlusion.

Quantitative analyses of diameter and running pattern of choroidal vessels in central serous chorioretinopathy by en face images.

This study was to investigate the choroidal vessels in eyes with central serous chorioretinopathy (CSC) quantitatively. We studied 41 CSC eyes and their fellow eyes, and 41 normal eyes of 41 age-adjusted individuals. En-face optical coherence tomography image of the top 25% slab of Haller's layer was analyze. The mean vessel area, vessel length, and vessel diameter were calculated. The running pattern of the vessels was quantified and used to determine the degree of symmetry, the "symmetry index". The vessel area of CSC eyes was not significantly different from that of fellow eyes but significantly larger than that of normal eyes. The vessel length of CSC eyes was not significantly different from fellow eyes but significantly shorter than that of normal eyes. The mean vessel diameter was larger in CSC eyes than in the fellow eyes and the normal eye. The symmetry index was not significantly different in CSC eyes from that of their fellow eyes but was smaller than that of normal eyes. The quantitative analysis showed that eyes with CSC had larger choroidal vessels and asymmetrical vessels running in Haller's layer.

Prediction of age and brachial-ankle pulse-wave velocity using ultra-wide-field pseudo-color images by deep learning.

This study examined whether age and brachial-ankle pulse-wave velocity (baPWV) can be predicted with ultra-wide-field pseudo-color (UWPC) images using deep learning (DL). We examined 170 UWPC images of both eyes of 85 participants (40 men and 45 women, mean age: 57.5 ± 20.9 years). Three types of images were included (total, central, and peripheral) and analyzed by k-fold cross-validation (k = 5) using Visual Geometry Group-16. After bias was eliminated using the generalized linear mixed model, the standard regression coefficients (SRCs) between actual age and baPWV and predicted age and baPWV from the UWPC images by the neural network were calculated, and the prediction accuracies of the DL model for age and baPWV were examined. The SRC between actual age and predicted age by the neural network was 0.833 for all images, 0.818 for central images, and 0.649 for peripheral images (all P < 0.001) and between the actual baPWV and the predicted baPWV was 0.390 for total images, 0.419 for central images, and 0.312 for peripheral images (all P < 0.001). These results show the potential prediction capability of DL for age and vascular aging and could be useful for disease prevention and early treatment.

Systemic and Ocular Determinants of Choroidal Structures on Optical Coherence Tomography of Eyes with Diabetes and Diabetic Retinopathy.

Knowledgeof the choroidal structures in eyes with diabetes and diabetic retinopathy (DR) should provide information on the pathogenesis of DR. A prospective study was performed to determine the systemic and ocular factors that affect the choroidal structures in eyes with diabetes. Two-hundred consecutive diabetic subjects consisted of 160 treatment-naïve patients with different stages of DR and 40 patients with proliferative DR with prior panretinal photocoagulation (PRP). All underwent blood and urine tests and enhanced depth imaging optical coherence tomography (EDI-OCT). The cross-sectional EDI-OCT images of the subfoveal choroid were binarized to measure the total choroidal area (TCA), luminal area, and stromal area. Multivariate regression analyses were performed to determine the systemic and ocular factors that were significantly correlated with the choroidal structures. The subfoveal choroidal thickness, TCA, luminal area, and stromal area were larger at more advanced stage of DR, and smaller in eyes with PRP than those without (P < 0.001). The TCA and stromal area were significantly and positively correlated with the degree of albuminuria (P = 0.034, P = 0.025, respectively). The choroidal lumen and stroma may increase as the stages of DR progress and decrease after PRP. Albuminuria may be associated with the choroidal stromal edema.

Comparative study on the structure and cytopathogenic activity of HIV Vpr/Vpx proteins.

The three-dimensional (3-D) structure of human immunodeficiency virus type 2 (HIV-2) Vpr/Vpx was predicted by homology modeling based on the NMR structure of human immunodeficiency virus type 1 (HIV-1) Vpr. The three proteins similarly have three major amphipathic alpha-helices. In contrast to HIV-1 Vpr, Vpr/Vpx of HIV-2 have a long N-terminal loop and clustered prolines in the second half of the C-terminal loop. HIV-2 Vpx uniquely contains a long region between the second and third major helices, and bears several glycines in the first half of the C-terminal loop. Instead of the glycines, there is a group of hydrophilic amino acids and arginines in the corresponding regions of the two Vprs. To compare the cytopathogenic potentials of HIV-1 Vpr and HIV-2 Vpr/Vpx, we examined the production of luciferase as a marker of cell damage. We further analyzed the characteristics of cells transduced with vpr/vpx genes driven by an inducible promoter. The results obtained clearly show that structurally similar, but distinct, HIV Vpr/Vpx proteins are detrimental to target cells.

Long-term outcome of vitrectomy for an idiopathic macular hole performed with the use of indocyanine green.

PURPOSE: To evaluate the long-term outcome and safety of vitrectomy for the treatment of an idiopathic macular hole using indocyanine green (ICG) to peel the internal limiting membrane(ILM). SUBJECTS AND METHODS: By means of a retrospective study, we evaluated the outcomes of 56 eyes in 56 patients with an idiopathic macular hole who all underwent a primary vitrectomy with successful closure of macular hole. We compared the outcomes of 35 eyes in 35 patients who underwent a vitrectomy with ICG-assisted ILM peeling to those of 21 eyes in 21 patients who underwent the same procedure without ILM peeling. The main outcomes were compared between preoperative and postoperative visual acuities. RESULTS: The periods to achieve the postoperative best visual acuity were 11.1 months in the ILM peeling group and 8.9 months in the non-ILM peeling group. However, there were no significant differences between the two groups regarding the postoperative best visual acuity and the final visual acuity. Complications related to ILM peeling with ICG were not found. CONCLUSION: These results support the safety of ILM peeling with ICG.