Background and Objective: Currently, there is no standardized formulation of intravenous anesthetic that exists for vitreoretinal surgery. We describe a novel anesthetic protocol for vitreoretinal surgery that is safe and effective for patients and surgeons alike. Study Design: Review the current challenges to vitreoretinal anesthetic technique and descriptive overview outlining the proposed anesthetic protocol and associated experience with technique. Results: The proposed anesthetic technique utilizes a sub-tenon peribulbar block with a continuous propofol infusion. A low dosage continuous propofol infusion provides patients with profound anxiolysis and relaxation while maintaining wakefulness. Fentanyl can be additionally titrated for patients that report symptoms of pain or increased respiratory rate. Conclusion: A low dose propofol infusion in combination with sub-tenon peribulbar block and judicious use of fentanyl provide an ideal operative condition for ambulatory vitreoretinal surgery. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:429–431.]

Purpose: Currently, no consensus exists on the role of optical coherence tomography (OCT) imaging in the setting of acute posterior vitreous detachment (PVD). The authors outline the clinical utility of OCT in the management of acute PVD and its complications. Methods: Literature review of OCT findings in association with acute PVD and report of illustrative cases. Results: Optical coherence tomography imaging in the setting of acute PVD can provide details of vitreoretinal interface that are difficult to appreciate on biomicroscopy alone including partial PVDs, focal vitreoretinal adhesions and traction, and subclinical macular changes. The presence of vitreous hyperreflective dots on OCT in the premacular space, especially if severe, is highly correlated with the presence of peripheral retinal breaks and development of epiretinal membrane. Advancements in OCT technology, including enhanced vitreous imaging OCT, swept-source OCT, wide-angle OCT, and widefield OCT, allow for increased resolution and expanded field of imaging of the vitreoretinal interface. Conclusion: Optical coherence tomography imaging is an emerging standard of care in the setting of patients presenting with new flashes and floaters. The authors highlight the benefits of OCT imaging in patients with acute PVD, which includes recognition of the status of the vitreoretinal interface, assistance in identifying high-risk PVDs, and performance of risk assessment that predict future macular pathologic condition.

Objective To understand patient burden of treatment of repeated intravitreal injections (IVI) in the management of exudative retinal diseases. Methods and analysis Participants were sampled from a large urban retina specialty practice in Houston, Texas, USA, based on history of ongoing receipt of IVI. The 50-item Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections questionnaire was developed to evaluate the patient experience including discomfort, anxiety, inconvenience and satisfaction. Categorial principal components analysis (CATPCA) was performed to assess construct validity and internal consistency. A subset of these items was used to establish a measure of total treatment burden, referred to as the IVI Treatment Burden Score (TBS). Results 142 patients participated in this study. CATPCA analysis revealed five dimensions of patient burden: disruption of normal routine or capacity, anxiety, frequency of visits, chronicity of disease and perceived treatment value or satisfaction. Together, these dimensions accounted for 67% of variance explained. Cronbach's alpha was 0.97. The most frequently cited cause of discomfort was the feeling after anaesthetic wore off. The most common source of anxiety was fear of injection and associated discomfort or pain. Regarding inconvenience, patients reported temporary postinjection debilitation, requiring an average of 8 hours for recovery per treatment. The most frequently identified sources of satisfaction were confidence in the provider or treatment and interactions with staff. Conclusions Understanding and quantifying the patient burden associated with repeated IVI for exudative retinal diseases can reveal opportunities to improve delivery methods. The TBS could serve to inform strategies to maximise treatment adherence and optimise patient experiences.

Ocular syphilis can occur at any time after initial infection and most commonly presents as posterior uveitis or panuveitis, although many other ocular findings have been documented. We present the case of a young, otherwise healthy Caucasian HIV-negative male who presented with acute onset of photopsias, floaters, and a rapidly progressive unilateral scotoma who was originally diagnosed with acute zonal occult outer retinopathy (AZOOR) and started on a high dose prednisone taper. Although his clinical symptoms improved on corticosteroids, he was later switched to Penicillin G treatment when his blood and cerebrospinal fluid (CSF) testing demonstrated syphilis as his underlying diagnosis. Given his ocular findings on the exam and reactive syphilitic testing, he was ultimately diagnosed with acute syphilitic posterior placoid chorioretinitis (ASPPC). Our patient's clinical improvement after a high-dose prednisone trial offers further evidence of an autoimmune component to the pathophysiology of ASPPC.

This case report highlights intermittent proptosis precipitated by exercise or Valsalva maneuvers. Conventional orbital computed tomography scan and catheter angiography did not disclose any orbital vascular lesion. Orbital B-scan ultrasonography, however, before and after a Valsalva maneuver demonstrated intermittent orbital vein dilation adjacent to the optic nerve of the left eye. Clinicians should be aware that anatomic venous variations and vascular malformations including orbital varices may produce a characteristic symptom of recurrent proptosis with Valsalva or head position. Conventional structural orbital imaging (e.g., computed tomography or magnetic resonance imaging) may not demonstrate a lesion.

Simultanagnosia is a well-known neurologic symptom characterized by the inability to conceptualize the whole picture despite being able to see individual elements within a visual scene. The pathophysiology involves a lesion to the bilateral parieto-occipital lobe. We report two unusual cases of simultanagnosia and juxtaposed homonymous visual field loss involving aqueductal stenosis-related obstructive hydrocephalus and cardiac arrest due to Brugada syndrome. Clinicians should be aware that simultanagnosia can be the presenting symptom of neuro-ophthalmic disease.

Neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD) are inflammatory disorders of the central nervous system characterized by severe, immune-mediated demyelination and axonal damage targeting the optic nerve and spinal cord (1). The autoimmune pathogenesis of NMO involves immunoglobulin G (IgG) antibody against aquaporin-4 (AQP4). AQP4 is a water-channel protein highly concentrated in the spinal cord gray matter, periaqueductal and periventricular regions, and the astrocytic foot processes (2). The hallmark presentation of NMO includes acute attacks of bilateral or rapidly sequential optic neuritis (ON, leading to severe visual loss) or transverse myelitis (TM, causing limb weakness, sensory loss, and bladder dysfunction) with a relapsing course (3). Relapse occurs within the first year after the initial event in 60 percent of patients and within 3 years in 90% (1). Other clinical presentations include brainstem symptoms, encephalopathy, fulminant demyelination, hypothalamic dysfunction, and posterior reversible leukoencephalopathy. In particular, the area postrema syndrome of nausea and vomiting or intractable hiccups occurs with an incidence of 16%–43% in NMOSD (4). We report a 57-year-old woman who presented with a serologically proven NMO exacerbation 25 years after her first unexplained episode of ON. This case documents an unusually long duration between episodes of recurrent ON in a patient with serologically confirmed NMO. Patients with unexplained ON, particularly those with lack of recovery, should be considered for testing for NMO antibody even decades after their initial ON event. A 57-year-old woman presented with acute painless visual loss in her right eye. This was associated with 3–4 episodes of a constant, dull headache localized to the left retrobulbar region. Family history was negative for multiple sclerosis (MS). The medical history was significant for anxiety, depression, and a remote history of recurrent ON in the left eye as her initial demyelinating episode in 1993. After this initial event, the patient experienced several similar episodes of visual loss in the left eye over the next 4 years. She had headache, left eye pain, and visual deterioration that progressively worsened with each episode. Each attack was treated with intravenous corticosteroids with some recovery until the last episode in 1996; this resulted in no light perception (NLP) vision in the left eye. The patient had no further episodes of ON or neurologic symptoms until the time of her current presentation (25 years after the initial episode). During the current episode of ON, serial cranial MRI scans, lumbar puncture, and laboratory testing for infectious and inflammatory etiologies were unrevealing. In retrospect, the patient had several unexplained bouts of nausea and hiccups before admission and was found asleep while sitting in a chair several times by her sister; she had not been diagnosed with narcolepsy. On neuro-ophthalmic examination, the visual acuities were 20/70 in the right eye and NLP in the left eye. Ocular motility was full. There was a left afferent pupillary defect (amaurotic pupil). Ophthalmoscopy demonstrated a normal optic disc on the right and optic atrophy in the left eye. MRI of the brain and orbits demonstrated contrast enhancement of the optic chiasm (Fig. 1). Lumbar puncture showed a normal opening pressure of 18-cm water and normal cerebrospinal fluid (CSF) cell counts, protein, glucose, and oligoclonal bands. CSF myelin basic protein was elevated and consistent with intrathecal production of immunoglobulin against myelin. The IgG albumin index, synthesis rate, and IgG were all elevated, consistent with breakdown of the blood–brain barrier. NMO AQP4-IgG serum antibody test was positive (1:10,000). The patient was started on methylprednisolone 1 g intravenously daily for 3 days before initiating intravenous immunoglobulin (IVIG). She received 4 days of IVIG before discharge.FIG. 1.: Coronal T1-weighted postcontrast MRI with fat suppression (A) and axial T1-weighted postcontrast MRI (B). Enhancement of the optic chiasm is noted (arrows).At the last follow-up at 1 month after presentation, the visual acuities had improved to 20/25 in the right eye but remained NLP in the left eye. Optical coherence tomography measurement of the peripapillary retinal nerve fiber layer thickness was 95 μm for the right eye and 38 μm for the left eye (Fig. 2). The macular ganglion cell layer demonstrated severe thinning in the left eye but was normal in the right eye.FIG. 2.: Optical coherence tomography scans of the optic nerves at 2 weeks after the patient's discharge from the hospital. The right optic nerve is normal with a peripapillary retinal nerve fiber layer thickness of 95 μm. The left optic nerve is diffusely pale with thinning of the retinal nerve fiber layer to 38 μm. INF, inferior; NAS, nasal; OD, right eye; OS, left eye; RNFL, retinal nerve fiber layer; SUP, superior; TMP, temporal.Our patient is unique in that course from the initial episode ON to the present attack that resulted in NLP vision occurred over a 25-year period. Unfortunately, the NMO AQP4-IgG antibody assay was not established until 2004 and did not exist at the time of our patient's multiple ON episodes in 1993. It is therefore unknown whether the patient's current seropositivity was present throughout her 25-year course. Interestingly, MRI of the cervical and thoracic spine demonstrated no cord involvement; the patient never had symptoms suggestive of transverse myelitis. Up to 50% of serologically positive patients with NMO, however, develop TM within 5 years of presentation, as many as 80% develop TM within 25 years (2). Patients with suspected NMO should be initially treated with high-dose intravenous methylprednisolone during acute attacks. F or patients with severe symptoms who are unresponsive to corticosteroids, therapeutic plasma exchange is the suggested rescue treatment. Plasma exchange has been demonstrated to be effective including in a randomized, double-masked clinical trial in patients with severe demyelinating disease (5). In contrast to evidence of a positive effect of plasma exchange, the efficacy of IVIG has not been clearly demonstrated in patients with NMOSD. Owing to the recurrent nature of NMO and the potentially poor recovery from attacks, long-term immunosuppression treatment is recommended for the prevention of attacks as soon as the diagnosis of NMO is made. Currently, there is no strict consensus on optimal drug regimen; however, azathioprine, rituximab, and mycophenolate mofetil are all considered first-line monotherapy treatment options. Immunosuppression in patients who are seropositive for AQP4 antibodies is usually continued for at least 5 years (and often indefinitely) because of the high risk of relapse or conversion to NMO (5). In conclusion, we describe a patient with serologically proven NMO manifesting as chiasmitis 25 years after an initial attack of ON. The current ON episode led to severe visual loss (NLP) in the left eye. This case is unique in having a long duration between the initial ON attack and the current episode of chiasmitis and the left eye visual loss. Clinicians should consider NMO in the differential diagnosis of any patient with acute ON even decades after an initial attack, especially when there is lack of recovery, bilateral involvement, or unusual MRI findings. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Rui Wang; b. Acquisition of data: Ashwini Kini; c. Analysis and interpretation of data: Ashwini Kini. Category 2: a. Drafting the manuscript: Rui Wang; b. Revising it for intellectual content: Bayan Al Othman; Category 3: a. Final approval of the completed manuscript: Andrew G. Lee.

Purpose: This study examines treatment-based outcomes of endophthalmitis due to antivascular endothelial growth factor (anti-VEGF) intravitreal injection and its effect on subsequent management of neovascular disease. Methods: A retrospective multicenter study was conducted of 157 patients with a diagnosis of endophthalmitis following anti-VEGF intravitreal injection at 10 major ophthalmic centers. Results: The median number of injections before endophthalmitis was 10 (range, 1 to 84 injections). Initial treatment with tap and inject with or without subsequent vitrectomy trended toward smaller visual acuity changes from baseline (4 ETDRS [Early Treatment Diabetic Retinopathy Study] letter difference vs 19 ETDRS letter difference) compared with initial vitrectomy, but the difference was not statistically significant. There was no significant change in medication choice among injections after endophthalmitis. There was a statistically significant shift away from regular interval (1- to 2-month) injections and a shift toward treat-and-extend and as-needed injection algorithms. Conclusions: The visual outcomes were not significantly different between patients who initially underwent tap and injection of antibiotics and those who underwent vitrectomy. There was no significant change in medication choice before and after endophthalmitis but there was a shift toward lower-frequency injection algorithms after postintravitreal injection endophthalmitis compared with prior.

Purpose: To describe the clinical and optical coherence tomography findings associated with the development of full-thickness macular holes after rhegmatogenous retinal detachment (RRD) repair.Methods: Retrospective, interventional case series. All patients who developed full-thickness macular holes after successful RRD repair from 3 clinical practices were reviewed. All cases of combined/simultaneous full-thickness macular hole and RRD were excluded. The main outcome measure was the presence of an epiretinal membrane at time of diagnosis of macular hole.Results: Twenty-five full-thickness macular holes were diagnosed after successful retinal detachment repair. Surgical approach to RRD repair included pneumatic retinopexy (6, 24%), scleral buckle alone (5, 20%), pars plana vitrectomy only (8, 32%), and combined scleral buckle and pars plana vitrectomy (6, 24%). The preceding RRD involved the macula in 19 patients (76%) before the formation of the macular hole. The median time to full-thickness macular hole diagnosis after RRD repair was 63 days (range, 4-4,080 days). An epiretinal membrane was present in all 25 (100%) macular holes. Two macular holes (8%) spontaneously closed, whereas the other 23 (92%) were successfully closed with a single surgical procedure. Mean visual acuity improved by approximately 5 lines to 20/72 (range, 20/20 to counting fingers at 1 foot) from 20/240 (range, 20/30 to hand motions) after macular hole repair (P < 0.0001).Conclusion: Full-thickness macular hole formation can occur after all types of RRD repair and is associated with an epiretinal membrane. The epiretinal membrane may play a role in the pathogenesis of secondary macular hole formation after RRD repair.

PURPOSE: To determine whether the efficacy and safety achieved with 2.0 mg intravitreal aflibercept injections (IAIs) for diabetic macular edema (DME) during the phase III VISTA DME trial were maintained with individualized, as-needed treatment.DESIGN: Phase IV, multicenter, open-label extension study.METHODS: Sixty patients completing VISTA DME elected to enter the ENDURANCE extension study. All patients received IAIs in the presence of clinically relevant DME. Patients were observed at 4-, 8-, or 12-week intervals depending on the need for treatment. Main outcome measures were mean IAIs given through month 12 (M12), the proportion of patients receiving no IAIs, and the role of macular laser in decreasing treatment burden among patients requiring ongoing IAIs.RESULTS: A mean of 4.5 IAIs were administered through M12. Eighteen (30%) patients required no IAIs, and among those who met IAI retreatment criteria, a mean of 6.0 IAIs were administered through M12. Best corrected visual acuity gains achieved during VISTA DME were maintained and stable with individualized dosing during ENDURANCE, fluctuating by < 1.5 mean letters from the baseline at all time points. Likewise, mean central retinal thickness remained relatively stable during ENDURANCE. Thirty-seven (62%) patients met macular laser criteria at a mean of 19.5 weeks with no significant difference in the frequency of IAIs before or after macular laser.CONCLUSION: Vision gains achieved during the 3-year VISTA DME trial were maintained through M12 of the ENDURANCE extension study with a reduced treatment frequency, with 30% of patients receiving no IAIs. No significant reduction in IAI frequency was observed after macular laser. application. (C) 2016 The Authors. Published by Elsevier Inc.

Retinal vein occlusion (RVO) typically results from thrombosis of venous outflow and potentially leads to retinal nonperfusion (RNP), release of vascular endothelial growth factor-A (VEGF), and secondary cystoid macular edema (CME). Despite advances in RVO management in the form of anti-VEGF and corticosteroid pharmaceuticals, many patients require repeated dosing. 1 Campochiaro P.A. Wykoff C.C. Singer M. et al. Monthly versus as-needed ranibizumab injections in patients with retinal vein occlusion: the SHORE study. Ophthalmology. 2014; 121: 2432-2442 Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar It is, therefore, clinically relevant to investigate approaches to reduce treatment burden in patients incompletely responsive to repeated intravitreal injections. One strategy is to combine anti-VEGF therapy with wide-field fluorescein angiography–guided targeted retinal photocoagulation (TRP) of peripheral areas of RNP. 2 Prasad P.S. Oliver S.C.N. Coffee R.E. et al. Ultrawide-field angiographic characteristics of branch retinal and hemicentral retinal vein occlusion. Ophthalmology. 2010; 117: 780-784 Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Photocoagulation of these regions may reduce pathologic VEGF levels, which may translate into diminished need for retreatment.

Purpose: To evaluate a prospective treat-and-extend (TREX) management strategy compared with monthly dosing with intravitreal ranibizumab (Lucentis) in neovascular age-related macular degeneration (AMD).Design: Prospective, randomized, multicenter clinical trial.Participants: Sixty patients with treatment-naive neovascular AMD randomized 1:2 to monthly or TREX cohorts.Methods: Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) of 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or, according to a TREX protocol, no less frequently than every 12 weeks. After interval extension, if recurrent exudative disease was identified, this maximum interval between treatments was rechallenged according to a strict prospective protocol.Main Outcome Measure: Change in ETDRS BCVA from baseline.Results: Sixty patients were enrolled and 50 completed month 24, at which point mean ETDRS BCVA letter gains were similar: 10.5 and 8.7 for the monthly and TREX cohorts, respectively (P = 0.64). At month 24, 4 patients (20%) and 12 patients (30%) in the monthly and TREX cohorts, respectively, gained at least 15 letters (P = 0.41). No monthly cohort patient lost more than 2 letters, whereas 5 TREX cohort patients (13%) lost at least 15 letters. Anatomic improvements were similar between the cohorts. Through month 24, the mean number of injections administered was 25.5 (range, 22-27) and 18.6 (range, 10-25) for the monthly and TREX cohorts, respectively (P < 0.001). Among TREX patients completing month 24, 14 (47%) were at an extension interval of 8 weeks or more, and the mean maximum tolerated extension was 8.5 weeks over the course of 2 years. Of the 26 TREX patients (65%) who demonstrated recurrent exudation upon interval extension, the first maximum extension interval was consistent in most eyes (n = 19 [73%]).Conclusions: The TREX neovascular AMD management protocol used with ranibizumab in the Treat-andExtend Protocol in Patients with Wet Age-Related Macular Degeneration (TREX-AMD) study resulted in visual and anatomic gains comparable with those obtained with monthly dosing, and most patients randomized to TREX therapy demonstrated a relatively consistent maximum extension interval. (C) 2016 by the American Academy of Ophthalmology.

Most mobile apps today require access to remote services, and many of them also require users to be authenticated in order to use their services.To ensure the security between the client app and the remote service, app developers often use cryptographic mechanisms such as encryption (e.g., HTTPS), hashing (e.g., MD5, SHA1), and signing (e.g., HMAC) to ensure the confidentiality and integrity of the network messages.However, these cryptographic mechanisms can only protect the communication security, and server-side checks are still needed because malicious clients owned by attackers can generate any messages they wish.As a result, incorrect or missing server side checks can lead to severe security vulnerabilities including password brute-forcing, leaked password probing, and security access token hijacking.To demonstrate such a threat, we present AUTOFORGE, a tool that can automatically forge valid request messages from the client side to test whether the server side of an app has ensured the security of user accounts with sufficient checks.To enable these security tests, a fundamental challenge lies in how to forge a valid cryptographically consistent message such that it can be consumed by the server.We have addressed this challenge with a set of systematic techniques, and applied them to test the server side implementation of 76 popular mobile apps (each of which has over 1,000,000 installs).Our experimental results show that among these apps, 65 (86%) of their servers are vulnerable to password brute-forcing attacks, all (100%) are vulnerable to leaked password probing attacks, and 9 (12%) are vulnerable to Facebook access token hijacking attacks.

AIM:To observe the effect of intravitreaI injection of Ranibizumab at perioperative period of compound trabecuIectomy on iris neovascuIarization, intraocuIar pressure ( IOP ) for patients with neovascuIar gIaucoma ( NVG) . METHODS: IntravitreaI injection of ranibizumab, compound trabecuIectomy and panretinaI photocoaguIation were given to 38 patients ( 38 eyes ) with neovascuIar gIaucoma, which couId not be controIIed by drugs, from January 2013 to January 2014 in Anyang Eye HospitaI. Iris neovascuIarization, IOP and changes of visuaI acuity were observed before and after treatments. The patients were foIIowed up for 6mo after treatments. RESULTS: Seven days after intravitreaI injection, 36 cases ( 94. 74%) had compIete regression of iris neovascuIarization. Two cases (5. 26%) had regression of smaII bIood vesseIs in the iris, a IittIe thick bIood vesseIs were remained. At 1mo after compound trabecuIectomy, iris neovascuIarization in aII patients were subsided; at 3mo after treatments, the iris neovascuIarization in 8 patients ( 21. 05%) were performed again, and accepted intravitreaI injection of ranibizumab again. Six months after the first treatments, aII patients showed no iris neovascuIarization. The mean IOP before injection was 42. 82 ± 10. 29mmHg. At 5d after the drug injection was 39. 13 ± 9. 71mmHg. Before and after the drug injection, change of IOP was not statisticaIIy significant (q=2. 65, P>0. 05). At 1wk,1,3 and 6mo after compound trabecuIectomy, IOP was 10. 53± 1.81mmHg, 10.11±1.73mmHg, 11.29±2.49mmHg, 12.58± 3. 01mmHg,which decreased significantIy (q=23. 15,23. 46, 22. 61, 21. 68, aII P<0. 01 ) compared with that before injection. Compared with the IOP at 5d after compound trabecuIectomy, the IOP at 1wk,1,3 and 6mo decreased significantIy (q=20. 51,20. 81,19. 96,19. 04, aII P<0. 01) . The success rate of compound trabecuIectomy was 73. 68%. FoIIowed up for 6 mo, visuaI acuity in 24 cases (63. 16%) improved and in 14 cases (36. 84%) remained unchanged. CONCLUSION: IntravitreaI injection of ranibizumab at perioperative period of compound trabecuIectomy can effectiveIy improve the success rate of the surgeries and reduce risk of compIications, and the effect is certainIy safe.

PURPOSE:To report macular photic trauma after accidental occupational exposure to a 750-nm Alexandrite laser and management of secondary choroidal neovascularization.METHODS:Institutional review board-approved retrospective case report.RESULTS:A 30-year-old woman presented with immediate vision loss in her left eye after direct inadvertent exposure to a single discharge from an occupational 750-nm Alexandrite laser used for laser hair removal. Baseline Snellen visual acuity was 20/40 in the involved left eye. One week after the initial exposure, the patient experienced subjective visual decline to 20/50, was treated with oral prednisone, and then developed a subretinal hemorrhage (SRH) in the setting of choroidal neovascularization 2 weeks later, or 3 weeks after initial trauma. The patient subsequently received 5 intravitreal ranibizumab injections over 25 weeks with resolution of the SRH. Final visual acuity was 20/50.CONCLUSION:The present case documents development and management of subretinal hemorrhage associated with choroidal neovascularization following macular photic trauma after accidental occupational to a 750-nm Alexandrite laser.

PURPOSE:To report the retinal findings and evolution of a visually symptomatic case of West Nile virus meningoencephalitis.METHODS:Case report. Main outcome measures include serologic testing for West Nile virus as well as longitudinal funduscopic examination, fluorescein angiography, and spectral domain optical coherence tomography.RESULTS:A 47-year-old diabetic man was referred for ophthalmic evaluation after hospitalization and treatment for West Nile meningoencephalitis. The patient presented with decreased vision and black spots in the right eye. Baseline visual acuity was 20/100 in the right eye and 20/40 in the left. Funduscopic examination and fluorescein angiography revealed multiple outer-retinal, punctate white spots in the macula and midperiphery of the right eye with no irregularities noted in the left eye. Spectral domain optical coherence tomography revealed granular hyperreflective specks casting variably dense shadows scattered throughout multiple retinal layers, most prominently within the outer and inner nuclear layers of the right eye. The patient was observed over the course of 14 weeks, and final visual acuity was 20/50 in the right eye. Longitudinally, the number of specks progressively decreased.CONCLUSION:During West Nile virus infection, granular hyperreflective specks located predominantly within the outer and inner nuclear layers were visualized by spectral domain optical coherence tomography and may be a sign of West Nile virus infection.

PURPOSE:To determine the rate of postintravitreal injection endophthalmitis and to assess microbiological features and outcomes with and without the use of peri-intravitreal injection topical ophthalmic antibiotics.METHODS:Consecutive series of endophthalmitis cases retrospectively identified after intravitreal injection at a multicenter, retina-only referral practice (Retina Consultants of Houston) from January 1, 2011 to December 31, 2014. Prophylactic peri-intravitreal injection topical antibiotics were routinely used during the initial 12-month period (January 1, 2011-December 31, 2011) and not used in the final 24-month period (January 1, 2013-December 31, 2014). Main outcome measures were incidence of endophthalmitis, microbiology results, treatment strategies, and visual outcomes.RESULTS:Of 90,339 intravitreal injections, 30 cases of endophthalmitis were identified (endophthalmitis rate = 0.033%; 95% confidence interval, 0.021-0.045%; or approximately 1 of 3,011 intravitreal injections). The most common organisms isolated were coagulase-negative staphylococci (n = 10, 33%), followed by Streptococcus mitis (n = 2, 7%). Fourteen cases (47%) were culture negative. Peri-intravitreal injection topical antibiotic prophylaxis did not decrease the rate of endophthalmitis (0.035% [95% CI, 0.007-0.064%] with antibiotic use versus 0.021% [95% CI, 0.008-0.033%] without antibiotic use; P = 0.261).CONCLUSION:The risk of endophthalmitis after intravitreal injection remains low, with coagulase-negative staphylococci and Streptococcus mitis the most common bacterial isolates identified. Prophylactic peri-intravitreal injection topical ophthalmic antibiotic use did not decrease the endophthalmitis rate.

Multiple myeloma (MM) is a plasma cell neoplasm that has a low apoptotic index. We investigated a new class of small molecules that target the terminal apoptosis pathway, called procaspase activating compounds (PACs), in myeloma cells. PAC agents (PAC-1 and B-PAC-1) convert executioner procaspases (procaspase 3, 6, and 7) to active caspases 3, 6, and 7, which cleave target substrates to induce cellular apoptosis cascade. We hypothesized that targeting this terminal step could overcome survival and drug-resistance signals in myeloma cells and induce programmed cell death. Myeloma cells expressed executioner caspases. Additionally, our studies demonstrated that B-PAC-1 is cytotoxic to chemotherapy-resistant or sensitive myeloma cell lines (n = 7) and primary patient cells (n = 11). Exogenous zinc abrogated B-PAC-1-induced cell demise. Apoptosis induced by B-PAC-1 treatment was similar in the presence or absence of growth-promoting cytokines such as interleukin 6 and hepatocyte growth factor. Presence or absence of antiapoptotic proteins such as BCL-2, BCL-XL, or MCL-1 did not impact B-PAC-1-mediated programmed cell death. Collectively, our data demonstrate the proapoptotic effect of B-PAC-1 in MM and suggest that activating terminal executioner procaspases 3, 6, and 7 bypasses survival and drug-resistance signals in myeloma cells. This novel strategy has the potential to become an effective antimyeloma therapy.

Purpose: To assess prospectively a treat-and-extend (TREX) management strategy compared with monthly dosing of intravitreal ranibizumab in treatment-naive neovascular age-related macular degeneration (AMD) patients.Design: Phase IIIb, multicenter, randomized, controlled clinical trial.Participants: Sixty patients with treatment-naive neovascular AMD randomized 1: 2 to monthly or TREX management.Methods: Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) from 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or according to a TREX protocol. The TREX patients were treated monthly for at least 3 doses, until resolution of clinical and spectral-domain optical coherence tomography evidence of exudative disease activity; the interval between visits then was individualized according to a strict prospective protocol.Main Outcome Measures: Mean ETDRS BCVA change from baseline.Results: At baseline, mean age was 77 years (range, 59-96 years), mean BCVA was 20/60 (Snellen equivalent), and mean central retinal thickness (CRT) was 511 mm. Fifty-seven eyes (95%) completed month 12, at which point mean BCVA improved by 9.2 and 10.5 letters in the monthly and TREX cohorts, respectively (P = 0.60). The mean number of injections administered through month 12 was 13.0 and 10.1 (range, 7-13) in the monthly and TREX cohorts, respectively (P < 0.0001). Among TREX patients, 7 (18%) were maximally extended, 4 (10%) demonstrated fluid at every visit, and at month 12, 18 (45%) had achieved an extension interval of 8 weeks or more; the mean maximum extension interval between injections after the first 3 monthly doses was 8.4 weeks (range, 4-12 weeks). Most TREX patients who demonstrated recurrent exudative disease activity (17/24 [ 71%]) were unable to extend beyond their initial maximum extension interval.Conclusions: The TREX neovascular AMD management strategy used in this prospective, randomized, controlled trial resulted in visual and anatomic gains comparable with those obtained with monthly dosing. Ophthalmology 2015; 122:2514-2522 (C) 2015 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).