Meibomian Gland Disease: The Role of Gland Dysfunction in Dry Eye Disease.

TOPIC: To discuss the pathology, causes, and ocular surface impact of meibomian gland disease (MGD), as well as its relationship to dry eye. CLINICAL RELEVANCE: MGD is a common disorder with various contributing mechanisms and clinical manifestations. Understanding MGD pathophysiology and its relationship to dry eye is important in order to optimize diagnosis and treatment algorithms. METHODS: A review of current literature was performed to discern MGD in terms of pathophysiology, risk factors, and ocular surface impact, and the relationship to dry eye. RESULTS: Meibomian gland obstruction and meibocyte depletion are important components of MGD. Many pathologies can disrupt function of meibomian glands, ranging from congenital to acquired causes. Once gland disruption occurs, the quality and quantity of meibum is altered, with a negative impact on the ocular surface. Increased tear evaporation, tear hyperosmolarity, increased ocular surface staining, increased inflammation, symptomatic irritation of the eyelid and globes, as well as decreased visual acuity have all been observed. CONCLUSION: MGD leads to changes in meibum quality and quantity that can cause evaporative dry eye and ocular surface disruption, leading to dry eye symptoms in some individuals.

Epidemiology of Herpes Zoster Ophthalmicus: Recurrence and Chronicity.

PURPOSE: A hospital-based epidemiology study to describe herpes zoster ophthalmicus (HZO) prevalence and risk factors for recurrent and chronic disease. DESIGN: Retrospective, hospital-based cohort study. PARTICIPANTS: All patients evaluated in the Broward and Miami Veterans Administration Healthcare System (MIAVHS) during the study period. METHODS: Retrospective medical record review of patients seen in the MIAVHS from January 1, 2010, through December 31, 2014, with a HZO clinical diagnosis. Assessment of the patient's clinical course was defined by the following: an acute episode of HZO was defined as quiescence of disease within 90 days of initial presentation, HZO recurrence was defined as any recurrent eye disease or rash 90 days or more after quiescence of disease was noted off therapy, and chronic HZO was defined as active disease persisting more than 90 days from initial presentation. MAIN OUTCOME MEASURES: Main outcome measures included the frequency of HZO with and without eye involvement, HZO recurrence rates, and risk factors for recurrent or chronic HZO. RESULTS: Ninety patients with HZO were included in the study. The mean age at incident episode of HZO was 68±13.8 years (range, 27-95 years). Most patients were white (73%), immune competent (79%), and did not receive zoster vaccination at any point during the follow-up (82%). Patients were followed for a mean of 3.9±5.9 years (range, 0-33 years). The period prevalence of HZ in any dermatome was 1.1%, the frequency of HZ involving V1 (HZO) was 0.07%, and the frequency of HZO with eye involvement was 0.05%. The overall 1-, 3-, and 5-year recurrence rates for either recurrent eye disease or rash were 8%, 17%, and 25%, respectively. Ocular hypertension (hazard ratio [HR], 4.6; 95% confidence interval [CI], 1.3-16.5; odds ratio [OR], 6.7; 95% CI, 1.5-31.2) and uveitis (HR, 5.7; 95% CI, 1.7-19.0; OR, 6.7; 95% CI, 1.5-31.2) increased the risk of recurrent and chronic disease. CONCLUSIONS: This study supports newer data indicating that a significant proportion of patients experience recurrent and chronic HZO. Further study is needed to guide preventative and therapeutic approaches to recurrent and chronic HZO.

Ocular and inflammatory markers associated with Gulf War illness symptoms.

To examine the utility of ocular coherence tomography (OCT) metrics, in conjunction with systemic markers of inflammation, in identifying individuals with Gulf War Illness (GWI) symptoms. Prospective case-control study of 108 Gulf War Era veterans, split into 2 groups based on the presence of GWI symptoms, defined by the Kansas criteria. Information on demographics, deployment history, and co-morbidities were captured. 101 individuals underwent OCT imaging and 105 individuals provided a blood sample which was analyzed for inflammatory cytokines using an enzyme-linked immunosorbent assay-based chemiluminescent assay. The main outcome measure was predictors of GWI symptoms, examined with multivariable forward stepwise logistic regression analysis followed by receiver operating characteristic (ROC) analysis. The mean age of the population was 55 ± 4, 90.7% self-identified as male, 53.3% as White, and 54.3% as Hispanic. A multivariable model that considered demographics and co-morbidities found that a lower inferior temporal ganglion cell layer-inner plexiform layer (GCL‒IPL) thickness, higher temporal nerve fiber layer (NFL) thickness, lower interleukin (IL)-1ß levels, higher IL-1α levels, and lower tumor necrosis factor-receptor I levels correlated with GWI symptoms. ROC analysis demonstrated an area under the curve of 0.78 with the best cut-off value for the prediction model having a sensitivity of 83% and specificity of 58%. RNFL and GCL‒IPL measures, namely increased temporal thickness and decreased inferior temporal thickness, respectively, in conjunction with a number of inflammatory cytokines, had a reasonable sensitivity for the diagnosis of GWI symptoms in our population.

Pyridostigmine Bromide Pills and Pesticides Exposure as Risk Factors for Eye Disease in Gulf War Veterans.

To examine associations between the pyridostigmine bromide (PB) pill and/or pesticide exposure during the 1990-1991 Gulf War (GW) and eye findings years after deployment. A cross-sectional study of South Florida veterans who were deployed on active duty during the GW Era (GWE). Information on GW exposures and ocular surface symptoms were collected via standardized questionnaires and an ocular surface examination was performed. Participants underwent spectral domain-ocular coherence tomography (SD-OCT) imaging that included retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and macular maps. We examined for differences in eye findings between individuals exposed versus not exposed to PB pills or pesticides during service. A total of 40.7% (n = 44) of individuals reported exposure to PB pills and 41.7% (n = 45) to pesticides; additionally, 24 reported exposure to both in the GW arena. Demographics were comparable across groups. Individuals exposed to PB pills reported higher dry eye (DE) symptoms scores (the 5-Item Dry Eye Questionnaire, DEQ-5: 9.3 ± 5.3 vs. 7.3 ± 4.7, p = 0.04) and more intense ocular pain (average over the last week: 2.4 ± 2.6 vs. 1.5 ± 1.8, p = 0.03; Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-E): 18.2 ± 20.0 vs. 10.8 ± 13.8, p = 0.03) compared to their non-exposed counterparts. DE signs were comparable between the groups. Individuals exposed to PB pills also had thicker OCT measurements, with the largest difference in the outer temporal segment of the macula (268.5 ± 22.2 µm vs. 260.6 ± 14.5 µm, p = 0.03) compared to non-exposed individuals. These differences remained significant when examined in multivariable models that included demographics and deployment history. Individuals exposed to pesticides had higher neuropathic ocular pain scores (NPSI-E: 17.1 ± 21.1 vs. 11.6 ± 12.9, p = 0.049), but this difference did not remain significant in a multivariable model. Individuals exposed to PB pills during the GWE reported more severe ocular surface symptoms and had thicker OCT measures years after deployment compared to their non-exposed counterparts.

Autoimmune Retinopathy, Testing, and Its Controversies.

Purpose of review: The purpose of this revision is to sumarize the most important clinical features of the autoimune retinopathies (AIRs). Recent findings: AIRs are a group of inflammatory conditions affecting the retina characterized by progressive unexplained visual loss, abnormalities and contraction in visual fields, photoreceptor and electroretinographic dysfunction, and the presence of circulating anti-retinal antibodies. The pathogenesis of AIR remains unclear and various antiretinal antibodies have been associated to the disease. The diagnosis of AIR is based on a particular clinical presentation along with the detection of serum antiretinal antibodies. Numerous anti-inflammatory therapeutic alternatives have been described for the treatment of AIR, nevertheless there is no consensus on treatment protocol. Summary: Because of its association with different types of malignant tumors, the early diagnosis, multi-disciplinary approach and prompt treatment should be warranted.

Optic Pit Maculopathy: Clinical Features and Management Options.

PURPOSE OF REVIEW: In this article, we review the pathogenesis, clinical features, imaging modalities and latest management options for optic pit maculopathy (OPM). RECENT FINDINGS: The pathogenesis of OPM remains to be unclear, but imaging tools such as optical coherence tomography (OCT) and OCT angiography are enhancing our knowledge. Observation continues to be the best management strategy for patients with good visual acuity, and many cases have demonstrated spontaneous resolution. For more advanced, progressive vision loss, treatment options involving vitrectomy can be considered and discussed with the patient. Supplementary techniques to vitrectomy have been reported in small studies with relative success such as glial tissue peeling, inverted internal limiting membrane flap, optic pit plugging, and retinal fenestration. SUMMARY: While there are multiple treatment options available for OPM, there is no consensus on the technique and surgical timing. Individual patient factors and the risks-benefits of treatment must be taken into account in guiding management. Larger clinical trials will further assist in decision making for treating OPM.

Ocular manifestations and biomarkers of Gulf War Illness in US veterans.

Gulf War Illness (GWI) is a multisystem disease with variable presentations, making diagnosis difficult. Non-invasive biomarkers would aid in disease diagnosis. We hypothesized that the eye could serve as a biomarker for GWI. We performed a retrospective case-control study using a sample of 1246 patients seen during a 5-month period in an optometry clinic. We identified veterans who were active duty during the Gulf War Era and either had a questionnaire-based diagnosis of GWI (cases) or did not (controls). Medical records were reviewed for eye and medical co-morbidities, medication use, and retinal macular and nerve fiber layer (NFL) thicknesses based on optical coherence tomography (OCT) images. Compared to controls (n = 85), individuals with GWI (n = 60) had a higher frequency of dry eye symptoms (50% vs 32.9%, p = 0.039). Multivariable analysis revealed average retinal NFL thickness (odds ratio; OR = 0.95), cup-to-disc ratio (OR = 0.005), age (OR = 0.82), and PTSD (OR = 20.5) were predictors of a GWI diagnosis. We conclude that GWI is associated with dry eye symptoms and RNFL thinning may serve as a biomarker for disease.

Peripapillary Halo in Inflammatory Papillitis of Birdshot Chorioretinopathy.

PURPOSE: Peripapillary halos (PPH) are peripapillary changes observed surrounding the optic nerve head in normal eyes and eyes with different disorders. Recognizing the microstructure and mechanism of development of these halos will help clinicians understand the different associated retinal and optic nerve head pathologies. We describe the in vivo histological characteristics of PPH in birdshot chorioretinopathy (BSCR). PATIENTS AND METHODS: This was a prospective observational case-series in a single tertiary referral center. Six eyes of three patients with PPH associated with BSCR were determined through clinical examination, fundus photography, and fundus autofluorescence (FAF). Patients underwent swept-source optical coherence tomography (SS-OCT) imaging of the optic nerve head and peripapillary region. RESULTS: In SS-OCT B-scans across the area of PPH, we observed thinning and interruption of retinal pigment epithelium (RPE)-Bruch's membrane complex. These halos are a circumferential form of alpha zone RPE-associated crescentic peripapillary atrophy (PPA), unlike the PPH observed with myopia and normal aging. CONCLUSION: PPH in BSCR patients may be a sign of prior inflammatory optic neuropathy.

Optical Coherence Tomography: Critical Tool to Manage Expectations after Cataract Extraction.

PURPOSE OF REVIEW: To review evidence on the utility of spectral domain optical coherence tomography (SD-OCT) in evaluating retinal structure prior cataract surgery and highlight new technologies that can assess retinal function perioperatively. FINDINGS: SD-OCT detected clinically unsuspected macular pathology in 4.6-25% of individuals in the pre-operative cataract evaluation. The most common findings were epiretinal membrane and macular degeneration with frequencies that varied by population studied. These conditions have been associated with complication after surgery (e.g. macular edema, visual dissatisfaction). As such, findings on SD-OCT may impact the informed consent process, alter IOL selection, and provide realistic postoperative vision expectations. Other technologies that assess retinal function, such as microperimetry and multifocal ERG are beginning to be studied but their utility in the pre-operative cataract evaluation is not yet known. SUMMARY: SD-OCT should be incorporated as a routine test prior to surgery to manage patient expectations and assist with optimal IOL selection, as even individuals with a seemingly normal clinical exam may have macular pathology. SD-OCT is the most established method for evaluating retinal anatomy and offers the benefits of a reduction in cases with missed macular pathology and fewer postoperative visual surprises.

A New Approach for Diabetic Macular Edema Treatment: review of clinical practice results with 0.19 mg fluocinolone acetonide intravitreal implant including vitrectomized eyes.

PURPOSE OF REVIEW: Fluocinolone acetonide is a synthetic fluorinated glucocorticoid. It has selective and potent agonist properties by binding to the cytosolic glucocorticoid receptor with high affinity; it is devoid of mineralocorticoid activity. Two extended-release (i.e. lasting up to 3 years) drug delivery systems containing fluocinolone acetonide (FAc) have been approved by the FDA for intravitreal use: Retisert ® (Bausch&Lomb, New Jersey, USA) and Iluvien ® (Alimera Sciences, Atlanta, USA). The former contains 0.59 mg of FAc, which is approved for the treatment of chronic noninfectious posterior segment uveitis. The latter contains a dose of 0.19 mg of FAc and is approved for the treatment of diabetic macular edema and here we review the results published in the clinical literature relating to its use in the treatment of diabetic macular edema (DME). RECENT FINDINGS: The 0.19 mg FAc implant (Iluvien®) is a new approved treatment approach for DME. It is a non-biodegradable implant that continuously releases a microdose of FAc into the vitreous cavity for up to three years. It is effective in chronic DME with the added value of decreasing the treatment burden of multiple intravitreal injections. Recently, clinical practice studies are reporting its efficacy and safety profile (intra-ocular pressure rise and cataract), as well as its use in clinical setting not included in clinical trial such as vitrectomized eyes. SUMMARY: The FAc implant has demonstrated in clinical practice results that mirror the results of the clinical trials efficacy wise. Regarding its safety profile, cataract is a common complication, however, intra-ocular pressure rises may be lower than the ones reported in trials. The implant has shown effectiveness in vitrectomized eyes. An increasing evidence of real-world studies have supported utility of the implant in DME patients. It's extended-release format for up to 3 years benefits to the patient and carer as it means fewer injections and visits to the clinic.

Impact and Trends in Global Ophthalmology.

Purpose of Review: Our goal is to provide a review of the impact, global estimates, and projection of vision impairment as well as ongoing systems for eye care delivery. Recent Findings: Many of the blinding diseases in developing countries are preventable or curable, but the lack of ophthalmologists, the lack of education, and the lack of access to any eye care are some of the major obstacles encountered. Summary: As our world becomes more interconnected through globalization, the interactions between different cultures and populations increase. Global ophthalmology is a field dedicated to building sustainable eye care delivery systems to deliver high-quality care in minimal resource settings, with the aim of reducing blindness around the world.

Ocular Manifestations of Sarcoidosis in a South Florida Population.

OBJECTIVE: To describe the ocular manifestations of sarcoidosis in a South Florida population and identify risk factors for the presence of ocular disease. DESIGN: Retrospective consecutive case series. METHODS: Medical charts of individuals with sarcoidosis seen in the University of Miami pulmonary department were reviewed for ocular disease. Odds ratios were used to identify risk factors for ocular sarcoidosis. RESULTS: Fourteen of 108 individuals with sarcoidosis had ocular involvement. The mean age of the 14 individuals was 56±15 years. Seventy-one percent were female, 50% were black, and 21% were Hispanic. Twelve had uveitis of which panuveitis was the most common subtype. Five had ≤20/70 vision in at least one eye due to uveitis. Neurosarcoidosis was a risk factor for ocular sarcoidosis (OR 6.14, p=0.03, 95% CI 1.21-31.09). CONCLUSION: Ocular manifestations occurred in a minority of individuals in a pulmonary sarcoidosis clinic in South Florida. Uveitis was the most common ocular manifestation. Neurosarcoidosis was a risk factor for ocular involvement.

Decision Making in Proliferative Diabetic Retinopathy Treatment.

PURPOSE OF REVIEW: The goal of this paper is to provide a comprehensive review of the recent advances in the management options for proliferative diabetic retinopathy. RECENT FINDINGS: For many years cases of proliferative diabetic retinopathy (PDR) have been managed by pan retinal photocoagulation (PRP). The advent of anti-vascular endothelial growth factor (anti-VEGF) agents has changed the future of PDR management and has provided an alternative to PRP. SUMMARY: Management of PDR requires the identification of high risk characteristics for PDR and the decision regarding the most appropriate treatment modality. The risk to benefit ratio for each treatment modality must be considered in determining the appropriate choice between surgical intervention (PRP) versus medical intervention with anti-VEGF.

Polypoidal Choroidal Vasculopathy.

PURPOSE OF REVIEW: The aim of this review is to summarize developments in the treatment of active polypoidal choroidal vasculopathy (PCV). PCV is associated with a poor visual prognosis as a consequence the condition's hallmark polypoidal dilatation and a branching network resulting in recurrent hemorrhages and serous leakage. RECENT FINDINGS: Recent research has provided new insights into the pathogenesis of PCV. While still considered a subtype of age-related macular degeneration, suggestions that PCV belongs to a spectrum of conditions that present with a pachychoroid are increasingly well accepted. Treatment remains challenging. Combination therapy (photodynamic therapy (PDT) and intravitreal anti-vascular endothelial growth factor (VEGF)) is associated with higher polyp closure rate, but polyp closure rate has not been correlated with superior visual outcomes. Current data points to non-inferiority of anti-VEGF alone versus combined with PDT when final vision acuity is the study outcome. SUMMARY: PCV remains a clinical challenge. Classification and treatment of the condition continues to evolve. Combination therapy may not be superior to anti-VEGF treatment alone in terms of visual acuity outcome, however data on long-term recurrence should be compared in formulating preferred treatment plans.

Retinal Arterial Macroaneurysms: Updating your Memory on RAM Management.

PURPOSE OF REVIEW: This is a comprehensive review of management options for retinal arterial macroaneurysms (RAMs). Although close observation is typically recommended for RAMs not involving or threatening the macula, other treatment modalities can be considered for exudative or hemorrhagic complications that are vision-threatening. RECENT FINDINGS: New imaging technologies like optical coherence tomography angiography (OCT-A) have been able to detect RAMs without the need of dye injection, further elucidating our understanding of blood flow within and around them. Observation alone is usually adequate treatment when lesion not threatening the fovea. Laser photocoagulation and intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors have effectively been used for management of exudative RAMs, whereas options including injection of VEGF inhibitors, tissue plasminogen activator (tPA), vitrectomy, gas, and yttrium aluminum garnet (YAG) laser have been used for hemorrhagic RAMs. SUMMARY: To date, there is no consensus regarding management of symptomatic exudative or hemorrhagic complications of RAM. Additionally, a case report is presented within this paper to illustrate the successful treatment of a hemorrhagic RAM in a symptomatic 65-year-old man using intravitreal bevacizumab.

Resolution of pain with periocular injections in a patient with a 7-year history of chronic ocular pain.

PURPOSE: We report a case of a male patient with chronic ocular pain that resolved completely following peripheral nerve blocks. OBSERVATIONS: A 66-year-old male presented with a seven-year history of severe left eye pain and photophobia. The pain began after retinal detachment repair with scleral buckle placement. Previous treatments included topical (autologous serum tears, corticosteroids, diclofenac, cyclosporine) and oral (gabapentin, diclofenac) therapies with no pain relief. The patient's pain was so severe that he requested enucleation. After discussion, the decision was made to perform periocular nerve blocks. Prior to the procedure, the patient reported an average pain intensity of 8 out of 10 and photophobia daily. Following left supraorbital, supratrochlear, infraorbital and infratrochlear injections with bupivacaine and methylprednisolone, pain intensity and photophobia improved to 1-2 out of 10. One week later, repeat infraorbital and infratrochlear nerve blocks were given, after which time the patient reported complete resolution of symptoms that lasted for 7 months. Repeat nerve blocks were administered with repeat resolution of pain. There were no complications associated with the procedures. CONCLUSIONS AND IMPORTANCE: Chronic ocular pain can be a debilitating condition. Periorbital nerve blocks can provide pain relief and should be considered as a potential treatment option after medical management has failed.

Effect of Anti-Vascular Endothelial Growth Factor Therapy on Corneal Nerves.

PURPOSE: Vascular endothelial growth factor (VEGF) is a trophic factor for corneal nerves (CNs). Despite its widespread use to treat a variety of retinal diseases, the effect of repetitive intravitreal (IV) anti-VEGF injections on CN is not known. METHODS: Retrospective case-control study. CN parameters were compared between eyes in 39 individuals who received anti-VEGF injections in one eye only. Next, we compared CN parameters between 50 eyes of 50 individuals with a history of IV anti-VEGF injections and 80 eyes of 80 individuals without a history of injection. In vivo confocal microscopic examination was conducted using the ConfoScan 4. Images were analyzed by the Corneal Nerve Analysis tool. Paired and independent t test methodologies were used to compare nerve parameters, and multivariable linear regression analysis was performed to control for potential confounders. RESULTS: In 39 patients (own controls), eyes with a history of IV injection had lower CN length density, total length, nerve fibers, bifurcations, and branches (P < 0.005) compared to the fellow eyes without injection. Similar findings were seen in the eyes of 50 individuals with a history of injection compared to 80 individuals without injection. A history of IV injections and ethnicity remained significantly associated with the CN length density and explained 32% of the variability (R = 0.56). CONCLUSIONS: We found decreased CN parameters in eyes with a history of anti-VEGF injections compared to eyes without such a history.

Predictive Value of the OCT Double-Layer Sign for Identifying Subclinical Neovascularization in Age-Related Macular Degeneration.

PURPOSE: Structural OCT images from eyes with nonexudative age-related macular degeneration (AMD) were graded for the presence of a double-layer sign to determine if the double-layer sign predicted subclinical macular neovascularization (MNV). DESIGN: Prospective, observational study. PARTICIPANTS: Nonexudative AMD patients with and without subclinical MNV identified by swept-source (SS) OCT angiography (OCTA). METHODS: Participants were enrolled prospectively into an SS OCTA imaging study. A set of test scans with and without subclinical MNV was compiled to assess the ability of trained graders to identify nonexudative type 1 MNV. The graders evaluated only the structural OCT B-scans of those eyes. The presence of a double-layer sign was used as a predictive sign for subclinical type 1 MNV. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) from 2 separate gradings were calculated and compared. MAIN OUTCOME MEASURES: The association between the presence of a double-layer sign and subclinical type 1 MNV. RESULTS: One hundred eyes with nonexudative AMD from 94 patients were used for this study. The test set contained 64 eyes with intermediate AMD, which included 20 eyes with subclinical MNV, and 36 eyes with late AMD, which included 13 eyes with subclinical MNV. Two junior graders read the scans separately then reached a consensus grading. They detected a double-layer sign in 24 of 33 eyes with subclinical MNV and did not detect a double-layer sign in 56 of 67 eyes without MNV. Their sensitivity, specificity, PPV, and NPV were 73%, 84%, 69%, and 86%, respectively. The senior grader detected a double-layer sign in 29 of 33 eyes with subclinical MNV and did not detect a double-layer sign in 58 of 67 eyes without MNV, achieving a sensitivity, specificity, PPV, and NPV of 88%, 87%, 76%, and 94%, respectively. For all graders, there were statistically significant associations between type 1 MNV and presence of the double-layer sign (P < 0.001). CONCLUSIONS: Presence of the double-layer sign on structural OCT B-scans was associated with subclinical type 1 MNV and can be used to identify these lesions with good predictive values in eyes with nonexudative AMD.

MUST Beg to Differ.

The authors provide a significant interpretation of the National Eye Institute-sponsored Multicenter Uveitis Steroid Treatment study, in which patients with severe, non-infectious intermediate, posterior, or panuveitis were randomly assigned to receive local treatment using the sutured intravitreal fluocinolone acetonide implant or systemic treatment consisting of oral steroids and conventional steroid-sparing immunosuppression, with a primary outcome of visual acuity at 2 years of follow-up. The authors also present evidence-based guidance for the treatment of noninfectious posterior segment involving uveitis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:266-268.].