The Vitreous Ecosystem in Diabetic Retinopathy: Insight into the Patho-Mechanisms of Disease.

Diabetic retinopathy is one of the leading causes of blindness in the world with the incidence of disease ever-increasing worldwide. The vitreous humor represents an extensive and complex interactive arena for cytokines in the diabetic eye. In recent decades, there has been significant progress in understanding this environment and its implications in disease pathophysiology. In this review, we investigate the vitreous ecosystem in diabetic retinopathy at the molecular level. Areas of concentration include: the current level of knowledge of growth factors, cytokine and chemokine mediators, and lipid-derived metabolites in the vitreous. We discuss the molecular patho-mechanisms of diabetic retinopathy based upon current vitreous research.

Endogenous Endophthalmitis: yield of the diagnostic evaluation.

BACKGROUND: Endogenous endophthalmitis is an infection of the eye secondary to sepsis, occurring in 0.04-0.5% of bacteremia or fungemia. Risk factors include intravenous drug abuse (IVDA), diabetes, indwelling catheters, and immune suppression. Many patients have known or suspected bacteremia or fungemia; however, culture yield is reported to be low (approximately 50%). The purpose of this study is to elucidate the yield of diagnostic evaluation including microbial cultures over a 6.5 year period at an academic center in the United States. METHODS: Retrospective chart review of patients with endogenous endophthalmitis at the University of Florida from June 2011 to February 2018. RESULTS: Included are 40 eyes of 35 patients. Endophthalmitis was secondary to an endogenous source in 23.5% of all endophthalmitis cases observed. Intraocular culture positivity was 28.6% overall but was 0% after initiation of systemic antibiotics. Most commonly identified organisms from the eye were coagulase-negative Staphylococcus and Candida. Blood culture positivity was 48.6%, most commonly Staphylococcus. IVDA was noted with increasing frequency as a risk factor. Diagnosis of endophthalmitis upon hospital admission was associated with a higher intraocular culture positivity (P = 0.040) and a shorter hospital stay (P = 0.035). Computed tomography (CT) and magnetic resonance imaging (MRI) were the highest yield imaging modalities; X-ray and non-ocular ultrasound were less diagnostically useful. Echocardiogram was positive by transesophageal route (TEE) in 22% and in 9% by transthoracic (TTE) testing. Following discharge from the hospital, 48.4% of patients failed to follow up with outpatient ophthalmology. CONCLUSIONS: Based on the results of this study, the interdisciplinary team should consider directed imaging, eye cultures prior to antimicrobial administration, thorough history for IVDA, and caution with premature discharge from the hospital.

Eicosanoid Profiles in the Vitreous Humor of Patients with Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy is a potentially blinding sequela of uncontrolled diabetes that involves a complex interaction of pro-angiogenic and inflammatory pathways. In this study, we compared the levels of pro-angiogenic arachidonic acid-derived mediators in human vitreous humor obtained from eyes with high-risk proliferative diabetic retinopathy versus controls. The results indicated that lipoxygenase and cytochrome P450-derived eicosanoids were elevated (5-HETE, 12-HETE, 20-HETE, and 20-COOH-AA), and there appeared to be no differences in levels measured in eyes with tractional retinal detachments versus those without. These results provide further insight into the pathogenesis of this disease and for the development of future potential therapeutic agents that target arachidonic acid metabolites to treat diabetic retinopathy.

Dosimetric dependence of ocular structures on eye size and shape for external radiation fields of electrons, photons, and neutrons.

The dosimetric dependence of ocular structures on eye size and shape was investigated within the standard ICRP Publication 116 irradiation geometries. A realistic transport geometry was constructed by inserting a scalable and deformable stylised eye model developed in our previous study within the head of the ICRP Publication 110 adult male reference computational phantom. Beam irradiations of external electrons, photons, and neutrons on this phantom were simulated using the Monte Carlo radiation transport code PHITS in the geometries of AP, RLAT, PA and ROT. Absorbed doses in ocular structures such as ciliary body, retina, and optic nerves were computed as well as that in lens. A clear dosimetric dependence of ocular structures on eye size and shape was observed for external electrons while only a small dependence was seen for external photons and neutrons. Difference of the tendency was attributed to their depth-dose distributions where spread dose distributions were created by photons and neutrons while more concentrated distributions were created by external electrons.

Retinal detachment, vitreous hemorrhage, and foveal hypoplasia associated with 3q27.1q27.2 microdeletion: a case report.

Terminal deletions of chromosome 3q are associated with a heterogenous clinical phenotype, which includes growth restriction, developmental delay, and intellectual disability. However, little has been published on the ophthalmic impacts of chromosome 3q deletions. We report a 9-year-old boy with a 1.4 megabase deletion of 3q27.1q27.2 whose ocular morbidities included retinal detachment in one eye, vitreous hemorrhage in the other eye, and foveal hypoplasia in both eyes that required acute care and continuous ophthalmologic follow-up.

Chronic ocular small vessel disease: An overview of diabetic retinopathy and its relationship with cardiovascular health.

Diabetic retinopathy (DR) is a potentially blinding disease originating from small vessel damage in the retina in chronic hyperglycemic states. DR has a complex multi-pathway driven pathogenesis resulting in diabetic macular edema and retinal ischemia, the former being the most common cause of vision impairment in DR. Hypoxia induced cytokines stimulate vascular endothelial growth factor (VEGF) production and subsequent angiogenesis with resultant mechanical retinal damage over time. Anti-VEGF therapy is effective for the treatment of center-involving diabetic macular edema. There is evolving evidence showing the effectiveness of anti-VEGF as both adjuvant and monotherapy in the treatment of proliferative DR, however laser photocoagulation continues to remain the standard of care. DR in large cohort studies has been shown to be an independent risk factor for the development of cardiovascular disease and mortality. In addition, changes in retinal vascular caliber ratios may have implications for risk of macrovascular events with a gender discrepancy towards women.

Exacerbation of pigment epithelial detachment following aflibercept: A case of bevacizumab rescue.

PURPOSE: We describe a 61-year-old female patient with a retinal pigment epithelial detachment (PED) of the left eye in the setting of neovascular aged-macular degeneration (nAMD) with unanticipated responses to aflibercept and bevacizumab. OBSERVATIONS: A reduction of PED size from 423 µm to 309 µm and vision improvement (20/150- to 20/40) were observed after five consecutive monthly injections of bevacizumab. A switch to aflibercept for the following two consecutive months showed an unanticipated incremental decline in vision (20/80- at month 1, 20/150- at month 2), increased PED size (749 µm), and the development of subretinal fluid (SRF). After a switch back to bevacizumab, the subretinal fluid resolved. After nine consecutive monthly injections of bevacizumab, final vision in the left eye was 20/25, and final PED height was 84 µm. CONCLUSIONS: Different anti-VEGFs may induce varied and unpredictable responses among the most recalcitrant cases of nAMD. Unpredictably, PED size in our patient worsened with aflibercept treatment. IMPORTANCE: Treatment for nAMD with large PEDs has poor level 1 evidence for guidance, and customized treatment should be considered.

Peripheral Retinal Neovascularization in a Patient with Sarcoidosis and Cocaine-Associated Autoimmunity.

A 63-year-old African-American female with history of sarcoidosis (lymph node biopsy proven) and cocaine abuse for 8 years was referred to us because of new floater. Her ocular history was unremarkable except for vague complaints of visual disturbance during a hospital admission in 2016. On presentation, her visual acuity was 20/400 in the right eye and 20/30 in the left eye. Dilated fundus exam and multimodal imaging showed thick epiretinal membrane (ERM) superior to optic nerve head causing a lamellar macular hole and intra retinal edema in the right eye, a full thickness macular hole, and peripheral neovascularization in the left eye. Peripheral vasculitis was appreciated in both eyes and peripheral neovascularization in the left eye on fluorescein angiography. The patient underwent laser therapy, and the new vessels regressed in the left eye without any changes in systemic medications. Multiple factors may contribute to retinal vasculitis and neovascularization including sarcoidosis, cocaine abuse, and other undiagnosed systemic vasculitis, which makes this case a mystery.

Bilateral anterior segment dysgenesis and persistent fetal vasculature associated with terminal 10q26 deletion.

Deletion of the 26q position on chromosome 10 results in a syndrome with well-documented systemic phenotypes. There are few reports of ophthalmic manifestations in terminal 10q26 deletion. We report a 4-week-old boy with terminal 10q26 deletion who had extensive ophthalmic abnormalities, including bilateral anterior segment dysgenesis and bilateral persistent fetal vasculature, with microphthalmia, microcornea, iris corectopia, congenital cataracts, and posterior embryotoxon.

Effect of pattern scanning laser on macular thickness in diabetic retinopathy.

PURPOSE: This study investigates the effect of pattern scanning laser (PASCAL) panretinal photocoagulation (PRP) on central macular thickness (CMT) and visual acuity (VA) in patients with proliferative diabetic retinopathy (PDR). METHODS: This retrospective non-randomized comparative case series included 262 eyes (163 with macular edema) of 177 patients with PDR. Treatment was PRP alone (137), PRP + anti-vascular endothelial growth factor (VEGF) (69), PRP + focal laser (28), or all three (89). CMT and central macular volume 3 and 6 mm from fovea were analyzed before and 1, 3, and 6 months after PRP. Spot number was plotted against CMT, and linear regression analysis was performed. RESULTS: For each treatment group and time point, there was a non-significant relationship between spot number and CMT. In eyes receiving all three treatment modalities, a significant negative relationship was found between spot number and 3-mm volume at 6 months (p = 0.04) and 6-mm volume at 1 month (p = 0.002) and 6 months (p = 0.011). There was no significant change in VA in any treatment group at the 6-month time point. CONCLUSION: PASCAL PRP ± focal laser or anti-VEGF was not associated with increased development of macular edema or change in VA. PASCAL PRP with focal laser and anti-VEGF may result in a decrease in macular edema.

Treatment of Recurrent Primary Cutaneous Mucinous Carcinoma of the Eyelid with Modified Wide Local Excision.

Primary cutaneous mucinous carcinoma (PCMC) is a rare, low-grade malignant neoplasm of the sweat gland, whose history has been controversial regarding eccrine versus apocrine origin. This case report describes a 53-year-old male who presented to the University of Florida, Gainesville, ophthalmology clinic and was referred to the oculoplastics service with a painless, subcentimeter mass on the lateral right upper eyelid including the canthus, consistent with recurrent primary cutaneous mucinous carcinoma of the eyelid. Four years prior, the patient had undergone excisional biopsy of the lesion in a clinic, which revealed residual tumor, but the patient deferred further surgery at the time. The patient underwent surgical excision of the mass with reconstruction without operative complications and with negative surgical margins. PCMC is difficult to diagnose clinically due to its rarity and requires a histopathological examination for confirmation of the diagnosis. This report presents the first case in the literature of primary cutaneous mucinous carcinoma in a patient with human immunodeficiency virus (HIV). With this case report, we aim to raise awareness of primary cutaneous mucinous carcinoma as a potential part of the differential diagnosis for malignant eyelid lesions, including those present in patients with HIV.

Utility of wound cultures in the management of open globe injuries: a 5-year retrospective review.

BACKGROUND: Endophthalmitis after open globe injury can be devastating to vision recovery. As treatment of endophthalmitis is often empiric, some surgeons may obtain cultures at presentation of trauma in anticipation of later infection. This study examines the usefulness of wound cultures obtained during globe repair. RESULTS: Institutional Review Board approval was obtained. Medical records were retrospectively reviewed, with 168 open globes included. Cultures of the wound site had been taken in all cases included in this study. Wound cultures were positive in 63% of cases but were not used for clinical decision-making for any patient in this study. Two patients had evidence of endophthalmitis at presentation, with results of vitreous culture matching those from the wound. No patient later developed endophthalmitis after open globe repair. CONCLUSIONS: Despite a high rate of wound contamination, few cases of endophthalmitis (1.2%) were seen in this series. In no case did the results of wound culture impact choice of antibiotic prophylaxis or treatment. Cultures obtained at the time of open globe repair were not cost effective in the subsequent management of the injury.

Surgical management of diabetic tractional retinal detachments.

Tractional retinal detachment is an end-stage form of diabetic retinopathy that occurs when contractile forces in the vitreous and neovascular tissue lead to the detachment of the neurosensory retina. We review the literature related to the management of this disease. Preoperative planning includes appropriate patient selection, diagnostic and prognostic imaging, and medical optimization with reduction of systemic risk factors. Use of antivascular endothelial growth factor for preoperative treatment has had significant benefits for tractional retinal detachment repair in improving surgical efficiency and outcomes. Advances in microsurgical instrumentation are discussed, with attention to small-gauge vitrectomy with improved flow dynamics, viewing strategies, and lighting allowing bimanual surgery. Special emphasis is placed on bimanual surgical technique, choice of tamponade, and the avoidance of iatrogenic damage. Complications and special considerations are further explored. Based on our compilation of relevant literature, we propose a surgical algorithm for the management of these complex patients.

Exercise band-induced lens dislocations: A case series.

PURPOSE: We report three cases of lens dislocation due to ocular trauma from a recoiling exercise band. OBSERVATIONS: Three patients had closed globe injury resulting in lens dislocation. All had previously undergone intraocular surgeries; two patients were within three weeks of pars plana vitrectomy for retinal detachment repair. Findings included vision loss, hyphema, and increased intraocular pressure refractory to medical management. The retina remained attached post-traumatically in all cases. Lens removal or repositioning resulted in improved vision. CONCLUSIONS AND IMPORTANCE: A recoiling exercise band can cause lens dislocation, hyphema, and ocular hypertension that may require surgical intervention. Our report emphasizes the importance of patient counseling in the perioperative period for the prevention of traumatic complications.

Multiloculated Ciliary Body Cysts and Lenticular Coloboma: A Rare Phenotypic Variation Associated With Persistent Fetal Vasculature.

A case of a 4 year-old boy with persistent fetal vasculature, lenticular coloboma, and a benign, multiloculated ciliary body mass is reviewed. The presence of ciliary body cysts in association with persistent fetal vasculature is sparsely reported. Its presence in a child can cause a diagnostic dilemma and lead to amblyopia. [J Pediatr Ophthalmol Strabismus. 2018;55:e39-e41.].

A scalable and deformable stylized model of the adult human eye for radiation dose assessment.

With recent changes in the recommended annual limit on eye lens exposures to ionizing radiation, there is considerable interest in predictive computational dosimetry models of the human eye and its various ocular structures including the crystalline lens, ciliary body, cornea, retina, optic nerve, and central retinal artery. Computational eye models to date have been constructed as stylized models, high-resolution voxel models, and polygon mesh models. Their common feature, however, is that they are typically constructed of nominal size and of a roughly spherical shape associated with the emmetropic eye. In this study, we present a geometric eye model that is both scalable (allowing for changes in eye size) and deformable (allowing for changes in eye shape), and that is suitable for use in radiation transport studies of ocular exposures and radiation treatments of eye disease. The model allows continuous and variable changes in eye size (axial lengths from 20 to 26 mm) and eye shape (diopters from -12 to +6). As an explanatory example of its use, five models (emmetropic eyes of small, average, and large size, as well as average size eyes of -12D and +6D) were constructed and subjected to normally incident beams of monoenergetic electrons and photons, with resultant energy-dependent dose coefficients presented for both anterior and posterior eye structures. Electron dose coefficients were found to vary with changes to both eye size and shape for the posterior eye structures, while their values for the crystalline lens were found to be sensitive to changes in only eye size. No dependence upon eye size or eye shape was found for photon dose coefficients at energies below 2 MeV. Future applications of the model can include more extensive tabulations of dose coefficients to all ocular structures (not only the lens) as a function of eye size and shape, as well as the assessment of x-ray therapies for ocular disease for patients with non-emmetropic eyes.

Intralenticular Ozurdex® - One Year Later.

Reported here is a case of intralenticular sustained-release dexamethasone implant (Ozurdex®, Allergan, Irvine, CA, USA) present for 1 year with effective treatment of refractory diabetic macular edema without rapid cataract formation. The crystalline lens remained stable for 12 months on exam despite the presence of the steroid-secreting foreign body. The diabetic macular edema resolved on exam and on optical coherence tomography. After 1 year, cataract extraction was uneventfully performed by phacoemulsification for a mild decline in visual acuity. Macular edema remains resolved 2 months following cataract removal. This is the longest reported period of observation of intralenticular Ozurdex in the literature. Ozurdex remains effective despite intralenticular location, and it can have minimal effects on cataract progression.