Disseminated Aspergillus lentulus Infection in a Heart Transplant Recipient: A Case Report.

We present the first published case of successfully treated disseminated Aspergillus lentulus infection in a solid organ transplant recipient with invasive pulmonary disease, endophthalmitis, and a cerebral abscess. This case highlights important challenges associated with treating A. lentulus, particularly regarding antifungal resistance and toxicities associated with long-term antifungal therapy.

Preclinical and clinical studies of photobiomodulation therapy for macular oedema.

AIMS/HYPOTHESIS: Diabetic macular oedema (DME) is the leading cause of visual impairment in people with diabetes. Intravitreal injections of vascular endothelial growth factor inhibitors or corticosteroids prevent loss of vision by reducing DME, but the injections must be given frequently and usually for years. Here we report laboratory and clinical studies on the safety and efficacy of 670 nm photobiomodulation (PBM) for treatment of centre-involving DME. METHODS: The therapeutic effect of PBM delivered via a light-emitting diode (LED) device was tested in transgenic mice in which induced Müller cell disruption led to photoreceptor degeneration and retinal vascular leakage. We also developed a purpose-built 670 nm retinal laser for PBM to treat DME in humans. The effect of laser-delivered PBM on improving mitochondrial function and protecting against oxidative stress was studied in cultured rat Müller cells and its safety was studied in pigmented and non-pigmented rat eyes. We then used the retinal laser to perform PBM in an open-label, dose-escalation Phase IIa clinical trial involving 21 patients with centre-involving DME. Patients received 12 sessions of PBM over 5 weeks for 90 s per treatment at a setting of 25, 100 or 200 mW/cm2 for the three sequential cohorts of 6-8 patients each. Patients were recruited from the Sydney Eye Hospital, over the age of 18 and had centre-involving DME with central macular thickness (CMT) of >300 µm with visual acuity of 75-35 Log minimum angle of resolution (logMAR) letters (Snellen visual acuity equivalent of 20/30-20/200). The objective of this trial was to assess the safety and efficacy of laser-delivered PBM at 2 and 6 months. The primary efficacy outcome was change in CMT at 2 and 6 months. RESULTS: LED-delivered PBM enhanced photoreceptor mitochondrial membrane potential, protected Müller cells and photoreceptors from damage and reduced retinal vascular leakage resulting from induced Müller cell disruption in transgenic mice. PBM delivered via the retinal laser enhanced mitochondrial function and protected against oxidative stress in cultured Müller cells. Laser-delivered PBM did not damage the retina in pigmented rat eyes at 100 mW/cm2. The completed clinical trial found a significant reduction in CMT at 2 months by 59 ± 46 µm (p = 0.03 at 200 mW/cm2) and significant reduction at all three settings at 6 months (25 mW/cm2: 53 ± 24 µm, p = 0.04; 100 mW/cm2: 129 ± 51 µm, p < 0.01; 200 mW/cm2: 114 ± 60 µm, p < 0.01). Laser-delivered PBM was well tolerated in humans at settings up to 200 mW/cm2 with no significant side effects. CONCLUSIONS/INTERPRETATION: PBM results in anatomical improvement of DME over 6 months and may represent a safe and non-invasive treatment. Further testing is warranted in randomised clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02181400 Graphical abstract.

Emerging corticosteroid delivery platforms for treatment of diabetic macular edema.

INTRODUCTION: Diabetic macular edema (DME) is a leading cause of vision impairment. Low-grade inflammation is thought to play a critical role in its pathogenesis. Although vascular endothelial growth factor inhibitors are used first-line, not all eyes with DME respond optimally and may respond better to corticosteroids. Currently corticosteroids for DME are given intravitreally and require regular monitoring. There is an unmet need for longer lasting therapies and/or effective noninvasive therapies such as those given via oral or topical routes. AREAS COVERED: This review discusses emerging corticosteroid delivery platforms for DME treatment. A literature search of investigational novel therapeutic steroid delivery platform in DME was conducted. Results are presented from preclinical, phase 1,2 & 3 clinical trials of various drug delivery systems using new technologies such as Solubilizing Nanoparticle technology, Mucus Penetrating Particles technology and Particle Replication In Non-wetting Templates. These new platforms aim to deliver corticosteroids effectively via topical, episcleral, subtenon, oral, and intravitreal routes. EXPERT OPINION: These novel drug delivery platforms have the potential to lead to noninvasive or minimally invasive therapies and may overcome the shortcomings of current pharmacotherapy. However, larger comparative trials are needed for these agents to be added to the current armamentarium in DME management.

RANIBIZUMAB AND AFLIBERCEPT FOR THE TREATMENT OF PIGMENT EPITHELIAL DETACHMENT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Data from an Observational Study.

PURPOSE: To assess the effect of intravitreal ranibizumab and aflibercept on retinal pigment epithelial detachment (RPED) in patients with neovascular age-related macular degeneration. METHODS: This was a retrospective analysis of data from a prospectively designed and implemented clinical audit. Analysis included change in RPED dimensions and visual acuity in 92/233 treatment-naive eyes with neovascular age-related macular degeneration and RPED 6 months after treatment with either aflibercept or ranibizumab. RESULTS: There was no significant between-group difference in the adjusted mean change for maximum RPED height (P = 0.195), diameter (P = 0.522) or visual acuity (P = 0.836) at 6 months. Injection frequency was the only clinical variable that affected RPED height (P = 0.050) and visual acuity change for both treatment groups (P = 0.004). Around 30% of eyes in each group had complete resolution of RPED at 6 months. CONCLUSION: Eyes with neovascular age-related macular degeneration and RPED showed significant functional and anatomical responses after 6 months of intravitreal anti-vascular endothelial growth factor injections. However, we found no significant difference in anatomical response or change in visual acuity between eyes treated with ranibizumab compared with aflibercept. Larger, prospectively designed, randomized studies with longer term follow-up may identify a difference between the two drugs that we did not detect.

Hypertensive eye disease: a review.

Hypertension is a risk factor for a number of vision-threatening eye conditions including retinal vascular occlusion, retinal macroaneurysm and non arteritic anterior ischaemic optic neuropathy. In addition, hypertension may exacerbate the vision-threatening effects of diabetic retinopathy and has been implicated in the pathogenesis of age-related macular degeneration. The effects of sustained hypertension are directly visible in the eye as hypertensive retinopathy and choroidopathy, reflecting a pathological process occurring throughout the body. Close collaboration between ophthalmologists and general practitioners/physicians is needed to ensure that hypertensive patients are identified and treated. Timely intervention in these patients may reduce the risk of both vision-threatening and systemic complications.

Reasons for discontinuation of intravitreal vascular endothelial growth factor inhibitors in neovascular age-related macular degeneration.

BACKGROUND: This study was aimed to identify the reasons for discontinuing intravitreal anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration. METHODS: This study is a retrospective chart review of a single Australian private practice. Analysis included patients who discontinued treatment from March 2006 to June 2012. RESULTS: Of 248 patients who commenced treatment, 105 (42.3%) had discontinued by June 2012. The reasons for discontinuation were available for 102 of the 105 (97.1%) patients. In 9 (3.6%) patients of the entire cohort, the doctor stopped the treatment as the lesion became inactive, whereas further treatment was thought to be futile in 27 (10.9%) patients. Twenty-six (10.5%) patients declined further treatment with 2 (0.8%) because of excessive treatment visits, 2 (0.8%) because of difficulty in attending, 2 (0.8%) because of the expense, 3 (1.2%) because of pain/discomfort, 6 (2.4%) thought that the treatment was not beneficial, and 11 (4.4%) had other medical conditions that were more severe. Treatment was discontinued in 40 (16.1%) patients for other reasons such as moving to another region in 27 (10.9%) and death in 11 (4.4%). CONCLUSION: These results indicate that the burden of intravitreal anti-vascular endothelial growth factor injections was a reason for treatment discontinuation in only a small minority of patients.

Potential intravenous immunoglobulin-induced optic disc edema.

Purpose: To report a case of recurrent and bilateral optic disc edema following intravenous immunoglobulin (IVIG) administration. Observations: A 46 year-old woman received IVIG on 3 separate occasions over 7 years for Non-Hodgkin's Lymphoma (NHL) and each time developed headaches and transient visual disturbance, and was subsequently found to have bilateral optic disc swelling. Lumbar puncture confirmed raised cerebrospinal fluid (CSF) opening pressure and there was resolution following treatment with oral acetazolamide (Diamox). Conclusions and importance: To our knowledge there is no literature on papilledema following administration of IVIG. This case is pertinent for physicians treating patients with IVIG who develop headache, transient visual disturbance and optic disc edema.

Optical Coherence Tomography Findings in Ocular Syphilis Involving the Posterior Segment of the Eye.

PURPOSE: To analyse posterior segment optical coherence tomography (OCT) findings in ocular syphilis. METHODS: Medical records of 54 patients presenting consecutively with syphilitic uveitis were reviewed. Vitreous, retina and choroid (one eye/patient) were assessed by spectral-domain OCT on presentation (54 eyes) and after treatment (31 eyes). Improvement in signs and associations between presenting signs and final best corrected visual acuity (BCVA) were determined by McNemar's and Fisher's exact tests. RESULTS: Early inner retinal OCT findings included hyperreflective dots (n = 49, 91%), tongue-like projections (n = 44, 81%) and large rounded spots (n = 41, 76%). Common outer retinal findings included thickening, irregularity, elevations and/or detachment of retinal pigment epithelium (n = 46, 85%), and disruption or loss of the ellipsoid zone (n = 33, 61%). Most outer retinal changes resolved with treatment (p < .05), and common presenting signs were not associated with poor final BCVA (p > .05). CONCLUSION: OCT findings have diagnostic value in ocular syphilis, but do not predict prognosis.

The electroretinogram in the genomics era: outer retinal disorders.

The inherited retinal diseases (IRDs) have traditionally been described phenotypically with the description evolving to incorporate more sophisticated structural and functional assessments. In the last 25 years there has been considerable advances in the understanding of underlying genetic aetiologies. The role of the ophthalmologist is now to work in a multi-disciplinary team to identify the disease-causing genotype, which might be amenable to gene-directed intervention. Visual electrophysiology is an important tool to assist the ophthalmologist in guiding the clinical geneticist to reach a final molecular diagnosis. This review outlines the physiological basis for the ISCEV standard electrophysiology tests, the role of electrophysiology in localising the functional deficit, correlation with structural findings to guide diagnosis and finally management of IRDs in the era of genomics with emphasis on the outer retina.

Outcomes of Suspending VEGF Inhibitors for Neovascular Age-Related Macular Degeneration When Lesions Have Been Inactive for 3 Months.

PURPOSE: Currently, little evidence supports the safety of suspending vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration (nAMD). We assessed the outcomes of eyes in which this seems to have been attempted. DESIGN: Observational study from a prospectively designed database. PARTICIPANTS: Eyes enrolled in the Fight Retinal Blindness! registry of nAMD treatment outcomes were considered to have suspended treatment if they had a 3-month or longer documented period of inactivity of the choroidal neovascular lesion with no further treatments unless the lesion re-activated. METHODS: Time and proportion to re-activation of the lesion were analyzed using Kaplan-Meier survival curves. Visual outcomes after treatment suspension were assessed with paired t tests. MAIN OUTCOME MEASURES: The proportion of eyes resuming treatment because of lesion re-activation, change in visual acuity (VA) at time of re-activation, and recovery of vision 12 months later. RESULTS: We identified 434 eyes in which treatment was suspended and that were tracked for at least 12 months thereafter. The estimated percentage of eyes re-activating in the first year after treatment suspension was 41%, increasing to 79% by the fifth year. The median time to re-activation was 504 days. The 275 eyes whose lesion was observed to re-activate lost a mean of 4.2 letters (95% confidence interval [CI], -5.6 to -2.8 letters; P < 0.001) from the last injection to the time of re-activation; 206 eyes resumed treatment for at least 12 months after re-activation and recovered a mean of +1.2 letters (95% CI, -0.4 to 2.7 letters; P = 0.133), resulting in a net loss of 3.3 letters (95% CI, 2.3-5.1 letters; P < 0.001) compared with VA at treatment suspension. Lower VA at the time of suspension and longer duration of treatment were associated with reduced risk of re-activation. Median time to re-activation was substantially greater when eyes had been treated for at least 3 years. CONCLUSIONS: Fewer than half of the eyes in which treatment was suspended re-activated in the first year, but most re-activated by the fifth year. Caution should be exercised to avoid suspending treatment prematurely. Further research is warranted to identify the eyes in which treatment may be suspended safely.

Macular oedema in idiopathic macular telangiectasia type 1 responsive to aflibercept but not bevacizumab.

We report a patient with macular oedema due to type 1 macular telangiectasia responding to intravitreal aflibercept injection. A 51-year-old man was diagnosed with type 1 idiopathic macular telangiectasia (IMT) in the right eye. The macular oedema was refractory to initial treatment with intravitreal bevacizumab and argon laser photocoagulation. The patient was then treated with intravitreal aflibercept injections, following which the macular oedema was completely resolved and his vision was significantly improved. Intravitreal aflibercept injection appears to improve vision and reduce persistent macular oedema secondary to type 1 IMT and demonstrated promising anatomical and visual outcomes.