Frank L. Brodie

Volume And Composition Of Reflux After Intravitreal Injection

Purpose: To quantify the amount of drug loss from cadaveric human eyes, which are injected via the pars plana with a known volume of dye at variable intraocular pressures. Methods: Eight cadaver eyes were divided into 2 intraocular pressure groups: normal (15 mmHg; 4 eyes) or high (30 mmHg; 4 eyes). Each eye was injected with 50 &mgr;L of hematoxylin dye, and the subsequent reflux was immediately collected on a Schirmer’s test strip. The test strip was scanned and digitally analyzed to determine the area of saturation and total color intensity present. Using a previously established equation, total volume of reflux and the amount of dye within that reflux were calculated. Results: The average total volume of refluxed fluid was 1.68 &mgr;L (median, 0.62 &mgr;L), with a range of 0 &mgr;L to 8.05 &mgr;L. The average volume of refluxed dye was 0.37 &mgr;L (median, 0.08 &mgr;L), with a range of 0 &mgr;L to 2.15 &mgr;L. On average, only 0.74% of the original 50 &mgr;L of injected dye was lost (median, 0.15%), with a range from 0% to 4.30%. Conclusion: Although the presence of subconjunctival bleb formation after intravitreal injection may be a concern to the clinician, data from the present study shows that only a very small amount of the injected therapeutic agent is lost in the reflux.

OBSTRUCTIVE SLEEP APNEA AND CENTRAL SEROUS CHORIORETINOPATHY

Purpose: The purpose of this study was to determine if there is an association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR). Methods: Patients with CSCR without a history of steroid use or secondary retinal disease were matched based on age/gender/body mass index with control patients and administered the Berlin Questionnaire to assess for OSA risk. Patients were scored “OSA+” if they were at “high risk” on the Berlin Questionnaire or reported a previous OSA diagnosis. Rates of OSA+ were compared between the 2 groups, odds ratio and its 95% confidence interval was calculated using exact conditional logistic regression. Results: Forty-eight qualifying patients with CSCR were identified. There were no statistically significant differences between the CSCR and control groups by age (mean = 55 years), gender (79% male), body mass index (mean = 28.2), history of diabetes, or hypertension. Within the CSCR group, 22 patients (45.8%) were OSA+ versus 21 control patients (43.8%) (difference = 2.1%; 95% confidence interval, −18.2% to 22.2%; exact odds ratio = 1.08, 95% confidence interval, 0.47–2.49; P = 1.00). Conclusion: When compared with matched controls, patients with CSCR did not have statistically significant higher rates of OSA risk or previous diagnosis. This finding contrasts with previous work showing a strong association between the diseases. The divergence is likely due to our matching controls for body mass index, a significant risk factor for OSA.

Retinal Structure in Cobalamin C Disease: Mechanistic and Therapeutic Implications

Abstract Purpose: To describe the retinal structure in a patient with cobalamin C (cblC) disease. Methods: A 13-year-old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). Results: The patient carried a homozygous (c.271dupA) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. At age 3 months he had a normal eye exam. A pigmentary maculopathy progressed to chorioretinal atrophy from 5–10 months. ERG at 7 months was normal. A nystagmus remained stable since the age of 2 years. At age 13, visual acuity was 20/250 (right eye) and 20/400 (left eye), with a +5.00 D correction, a level of vision maintained since first measurable at age 5 years. SD-OCT showed bilateral macular coloboma-like lesions; there was also a thickened surface layer with ganglion cell layer thinning. Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL) transitioned to regions with no discernible ONL with a delaminated, thickened, inner retina. Conclusions: A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma-like lesions suggest there may be an interference with retinal/foveal development in cblC, a mechanism of maculopathy that may be shared by other early onset retinal degenerations. Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration.

Corneal Injury from Presurgical Chlorhexidine Skin Preparation

BACKGROUND Chlorhexidine skin preparation has been shown to provide highly effective antimicrobial presurgical skin cleansing. However, there is a significant risk of ocular toxicity when it is used in periocular areas. CASE DESCRIPTION We describe 2 cases of significant corneal damage resulting from 4% chlorhexidine gluconate preoperative skin cleanser, despite the use of protective occlusive dressing over the eyes. Because of the potential for severe corneal toxicity resulting from use of chlorhexidine, alternative agents such as 10% povidone-iodine should be considered for skin preparation near periocular areas whenever possible. CONCLUSIONS If chlorhexidine gluconate must be employed near periocular areas, great care must be exercised to avoid contact with the eyes, and additional protective measures (e.g., absorbent eye pads along with tightly occlusive dressings) must be used whenever possible.

A Novel Method for the Measurement of Reflux from Intravitreal Injections: Data from 20 Porcine Eyes

Abstract Background: Reflux following intravitreal injection is a common phenomenon, but it is unknown how much, if any, medication is lost as a result. Reflux is known to be a combination of vitreous and the injected agent, but the relative composition is unknown. This article describes a novel method for the measurement of the volume and composition of reflux and presents data from porcine eyes. Methods: Twenty porcine eyes were injected with 0.05 ml of dye at intraocular pressures (IOPs) of 15, 20, 25 and 30 mmHg (five eyes per subgroup). Reflux was captured on filter paper and the area of saturation and color intensity of the dye were digitally analyzed. Total refluxed volume and proportion of dye versus vitreous fluid were calculated from linear regression lines created from known standards. Results: Average (median) total volume of reflux from all eyes was 1.19 μl (0.93 μl), volume of injected dye refluxed was 0.47 μl (0.11 μl) and composition of reflux was 20.8% dye (15.5%). Less than 1% of the injected dye was lost to reflux. There were no differences between IOP groups in the total volume refluxed, the total amount of dye refluxed, the average composition of the reflux or the amount of injected dye refluxed (df = 3 for all comparisons; p = 0.58, p = 0.51, p = 0.55, p = 0.51, respectively). Conclusions: This novel method allows for measurement of quantity and composition of reflux following intravitreal injection in vitro. While reflux occurs frequently, it is predominantly composed of vitreous, not the injected agent. In fact, <1% of the original injection was lost to reflux.

How Was Your Sleep? New Implications for Obstructive Sleep Apnea in Retinal Disease.

How Was Your Sleep? New Implications for Obstructive Sleep Apnea in Retinal Disease It is not uncommon for patients to wonder how well rested their surgeon is; conversely, it is increasingly clear that we should be asking the same of our patients. Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that has been implicated as a risk factor for an increasing number of systemic and ophthalmic diseases. Consensus estimates place the prevalence of OSA at 25% of American men and 10% of American women. Obstructive sleep apnea occurs as a result of repeated upper airway collapse during sleep. In patients with OSA, there is collapse of the airway secondary to either anatomic narrowing or as a result being compressed by increased neck girth. It has been shown repeatedly that increasing age and body mass index are strong risk factors for OSA. As a result of repeated upper airway collapse, OSA is characterized by recurrent apneic periods during sleep with corresponding transient hypoxia. Repeated hypoxic episodes upregulate sympathetic drive and create significant blood pressure lability. In addition, OSA-induced hypoxia and subsequent reperfusion of tissue can cause reperfusion injury with endothelial dysfunction and inflammation. As a result, OSA leads to systemic vascular complications. Specifically, OSA has been associated with significantly increased risk of cardiovascular mortality, stroke, Type 2 diabetes mellitus, and chronic kidney disease. The first described effect of OSA on the eye was the mechanical rubbing on eyelids from sleeping in a supine position, causing floppy eyelid syndrome. More recently, OSA has been implicated in increasing risk of ischemic optic neuropathy. In 1998, Mojon et al first proposed a relationship between OSA and nonarteritic ischemic optic neuropathy. Subsequent studies bore out this relationship, suggesting an over twofold increase in risk for nonarteritic ischemic optic neuropathy in patients with OSA. Obstructive sleep apnea has also been associated with glaucoma, with several smaller studies suggesting a relationship. However, in a larger subsequent study of 228 patients with OSA, the prevalence of glaucoma was 2%, similar to the prevalence in the general population. Similarly, a large multicenter study in France reviewed the records of nearly 10,000 patients and after elimination of confounders such as age, no relationship between glaucoma and OSA was found. The role of OSA in diabetic retinopathy is becoming increasingly apparent. Although OSA and Type 2 diabetes mellitus share many common risk factors, studies show that OSA is an independent risk factor for the development and progression of diabetic retinopathy. More than simply increasing the risk for ophthalmic disease, recent work suggests OSA might hamper the therapeutic benefits of antivascular endothelial growth factor (anti-VEGF) therapy. Retinal specialists have struggled to understand why a subset of patients with diabetic macular edema and age-related macular degeneration (AMD) fail to respond to anti-VEGF therapy. A variety of mechanisms have been proposed including tachyphlaxis, genetic variation, and anatomic differences between neovascular lesions. Last year, Nesmith et al proposed a relationship between anti-VEGF nonresponders and OSA. They showed that for patients with either diabetic macular edema or wet AMD, poor response to anti-VEGF therapy was correlated with a higher incidence of OSA symptoms. Patients with wet AMD who had persistent subretinal fluid by optical coherence tomography after three anti-VEGF injections had more symptoms suggestive of OSA than patients who responded successfully to the injections. Similarly, those patients who required the largest number of intravitreal injections to treat diabetic macular edema had a higher prevalence of OSA symptoms than patients whose diabetic macular edema resolved quickly with anti-VEGF therapy. Because this study was cross-sectional, the ability to demonstrate causation was limited. Additionally, only symptoms of OSA were ascertained (by self report); diagnosis of OSA requires inpatient overnight polysomnography, which was not done in that study. In this issue, a study by the same group provides stronger evidence that the presence of OSA impacts The author has no financial/conflicting interests to disclose.

Time-reversed ultrasonically encoded optical focusing through highly scattering ex vivo human cataractous lenses

Abstract. Normal development of the visual system in infants relies on clear images being projected onto the retina, which can be disrupted by lens opacity caused by congenital cataract. This disruption, if uncorrected in early life, results in amblyopia (permanently decreased vision even after removal of the cataract). Doctors are able to prevent amblyopia by removing the cataract during the first several weeks of life, but this surgery risks a host of complications, which can be equally visually disabling. Here, we investigated the feasibility of focusing light noninvasively through highly scattering cataractous lenses to stimulate the retina, thereby preventing amblyopia. This approach would allow the cataractous lens removal surgery to be delayed and hence greatly reduce the risk of complications from early surgery. Employing a wavefront shaping technique named time-reversed ultrasonically encoded optical focusing in reflection mode, we focused 532-nm light through a highly scattering ex vivo adult human cataractous lens. This work demonstrates a potential clinical application of wavefront shaping techniques.

Performance of Bio-Occlusive Dressing as Barrier Protection from Presurgical Chlorhexidine Skin Preparation

ABSTRACT Purpose/Aim of the study: Chlorhexdine has been shown to provide excellent and cost-effective presurgical antisepsis. However, standard presurgical concentrations of chlorhexidine (2–4%) are known to cause ocular injury, even in cases in which a bio-occlusive dressing (Tegaderm™) was applied beforehand to the closed eye. Materials and Methods: Three experiments were conducted to assess the barrier performance of Tegaderm™ to chlorhexidine skin prep in vitro and on non-ocular skin. The experiments used water as a control group. Results: In the first in vitro experiment, the chlorhexidine group showed penetration at the edges of the Tegaderm™ at 5 minutes while the water (control) group never penetrated the Tegaderm™. A subsequent experiment testing the central permeability of the tegaderm showed it to be impermeable to both chlorhexidine and water after 90 minutes. In the in vivo experiment, the chlorhexidine group showed penetration at 10 minutes, while the water (control) group never penetrated the Tegaderm™. Conclusions: These data suggest Tegaderm™ is permeable at the edges to chlorhexidine but not water. Based on this, along with reports of ocular injury from chlorhexidine skin preparation of the head despite prior application of Tegaderm™ over the eyes, we advise against using bio-occlusive adhesive dressing to protect the ocular surface from chlorhexidine exposure. We suggest an alternative presurgical antiseptic agent such as povidone-iodine be employed whenever possible.

Anxiety in patients undergoing cataract surgery: a pre- and postoperative comparison

Purpose Reducing surgery-related patient anxiety without under-emphasizing surgical risk is challenging for even the most experienced surgeon. The purpose of this study is to identify specific anxieties faced by patients in hopes of better informing the preoperative surgeon-patient dialogue. Setting Comprehensive and specialty ophthalmology clinics at the University of California, San Francisco. Design A prospective, survey-based study in which a pre- and postoperative questionnaire was administered to patients undergoing routine phacoemulsification. The surgeon was masked to patient enrollment and questionnaire responses. Materials and methods A 36-item questionnaire on patient anxiety was developed from existing literature, building on the validated Surgical Fear Questionnaire. Patients were eligible if they were aged >18 years and willing to participate. Patients were excluded if having more than phacoemulsification alone or if unable to respond in English, and were retroactively excluded if there were complications during surgery. The primary outcome was self-reported anxiety on an 11-point Likert scale. Results Sixty-one patients were included for analysis. Preoperatively, patients reported greatest anxiety around the operation itself and becoming blind. Reflecting postoperatively, patients reported the greatest anxiety for the operation itself. Statistically significant decreases were greatest for anxiety about the operation failing (p<0.001) and becoming blind (p<0.001). No decrease was observed for the operation itself (p=0.1). Conclusion More effort must be made to specifically discuss the steps of the operation itself and the expected visual outcomes to alleviate patient anxiety. The authors hope these data can provide insight for surgeons into patient anxiety surrounding cataract surgery and help strengthen the patient–physician relationship.

Novel positioning sensor with real-time feedback for improved postoperative positioning: pilot study in control subjects

Introduction Repair of retinal detachment frequently requires use of intraocular gas. Patients are instructed to position themselves postoperatively to appose the intraocular bubble to the retinal break(s). We developed a novel wearable wireless positioning sensor, which provides real-time audiovisual feedback on the accuracy of positioning. Methods Eight healthy volunteers wore the wireless sensor for 3 hours while instructed to maintain their head tilted toward the 2 o’clock meridian with no audiovisual feedback. Positioning accuracy was recorded. The subjects repeated the experiment for 3 hours with the audiovisual feedback enabled. Results With no audiovisual feedback, the percentage of time greater than 10° out of position varied from 8.9% to 93.9%. With audiovisual feedback enabled, these percentages ranged from 9.4% to 65%. Three subjects showed significant improvement in their time out of position (P<0.01, Fisher’s exact test). Four subjects demonstrated a nonsignificant improvement, and one subject had a significant increase in time out of position with feedback (P<0.01). When pooled, all subjects demonstrated a statistically significant decrease in degrees out of position (P<0.001, Wilcoxon test) and a statistically significant improvement in total time out of position (P<0.001). Conclusion The novel positioning sensor showed improved positioning compliance in half of the healthy volunteers during our short pilot study. Other subjects derived little benefit from the feedback. The causes for this observation are unclear. However, given the significant improvement as a group, this new technology could be beneficial to patients who struggle with postoperative positioning.