The Fate and Prognostic Implications of Hyperreflective Crystalline Deposits in Nonneovascular Age-Related Macular Degeneration.

Purpose: To explore patterns of disease progression in nonneovascular age-related macular degeneration (AMD) associated with hyperreflective crystalline deposits (HCDs) in the sub-retinal pigment epithelium-basal laminar space. Methods: Retrospective review of medical records, multimodal imaging, and longitudinal eye-tracked near-infrared reflectance (NIR) and optical coherence tomography (OCT) spanning ≥2 years. NIR/OCT images were analyzed with ImageJ software to identify HCD morphology and location. Associated macular complications were reviewed from the time of HCD detection to the most recent follow-up, using NIR/OCT. Results: Thirty-three eyes with HCDs from 33 patients (mean age: 72 ± 7.5 years) had 46.7 months (95% confidence limits: 33.7, 59.6) of serial eye-tracked NIR/OCT follow-up. Baseline best-corrected visual acuity (BCVA) was 0.44 logMAR (Snellen equivalent 20/55). At a mean of 11.3 months (3.1, 19.6) after HCD detection, 31/33 (93.9%) eyes had developed macular complications including de novo areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in 21/33 (64%) eyes, enlargement of preexisting cRORA in 4/33 (12%) eyes, and incident macular neovascularization in 3/33 (9%) eyes. Movement and clearance of HCDs in 9/33 (27%) eyes was associated with enlargement of preexisting cRORA (r = 0.44, P = 0.02). BCVA at the last follow-up visit had decreased to 0.72 logMAR (20/105). Conclusions: Eyes with nonneovascular AMD demonstrating HCDs are at risk for vision loss due to macular complications, particularly when movement and clearance of these structures appear on multimodal imaging. HCD reflectivity and dynamism may be amenable to automated recognition and analysis to assess cellular activity related to drusen end-stages.

Comparative efficacy of unique antiepileptic drug regimens in focal epilepsy: An exploratory study.

OBJECTIVE: To compare efficacy of unique antiepileptic drug (AED) polytherapy regimens among patients with focal epilepsy. METHODS: From a longitudinal study of AED treatment, we identified patients with active focal epilepsy who had attempted at least two unique AED regimens (mono-, duo-, or tri-therapy). Efficacy was defined as the presence of at least one six-month period of continuous seizure freedom during exposure to a regimen. To control for individual variations in response and epilepsy severity, we used within-patient comparison approaches, in which we: 1) compared head-to-head unique regimens tried within the same patients; 2) compared one regimen versus aggregate of other regimens attempted in that patient; and 3) compared aggregated monotherapy versus polytherapy regimens. RESULTS: 757 patients met our criteria and had collectively attempted 170 unique regimens. In the head-to-head analysis, lamotrigine monotherapy was more effective than phenytoin monotherapy. Two regimens were more effective than the aggregate of other regimens attempted: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Two other regimens exhibited slightly better efficacy but did not reach statistical significance: clobazam/levetiracetam/lamotrigine and levetriacetam/oxcarbazepine. Patients who previously attempted at least four regimens had slightly better outcomes on polytherapy than monotherapy, though this was not significant. SIGNIFICANCE: We identified two unique regimens more likely to be associated with ≥6 months of seizure freedom: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Polytherapy may be an effective alternative to monotherapy for patients with focal epilepsy and persistent seizures.

Prevalence and risk factors of seizure clusters in adult patients with epilepsy.

PURPOSE: In the current study, we explored the prevalence of physician-confirmed seizure clusters. We also investigated potential clinical factors associated with the occurrence of seizure clusters overall and by epilepsy type. METHODS: We reviewed medical records of 4116 adult (≥16years old) outpatients with epilepsy at our centers for documentation of seizure clusters. Variables including patient demographics, epilepsy details, medical and psychiatric history, AED history, and epilepsy risk factors were then tested against history of seizure clusters. Patients were then divided into focal epilepsy, idiopathic generalized epilepsy (IGE), or symptomatic generalized epilepsy (SGE), and the same analysis was run. RESULTS: Overall, seizure clusters were independently associated with earlier age of seizure onset, symptomatic generalized epilepsy (SGE), central nervous system (CNS) infection, cortical dysplasia, status epilepticus, absence of 1-year seizure freedom, and having failed 2 or more AEDs (P<0.0026). Patients with SGE (27.1%) were more likely to develop seizure clusters than patients with focal epilepsy (16.3%) and IGE (7.4%; all P<0.001). Analysis by epilepsy type showed that absence of 1-year seizure freedom since starting treatment at one of our centers was associated with seizure clustering in patients across all 3 epilepsy types. In patients with SGE, clusters were associated with perinatal/congenital brain injury. In patients with focal epilepsy, clusters were associated with younger age of seizure onset, complex partial seizures, cortical dysplasia, status epilepticus, CNS infection, and having failed 2 or more AEDs. In patients with IGE, clusters were associated with presence of an aura. Only 43.5% of patients with seizure clusters were prescribed rescue medications. CONCLUSION: Patients with intractable epilepsy are at a higher risk of developing seizure clusters. Factors such as having SGE, CNS infection, cortical dysplasia, status epilepticus or an early seizure onset, can also independently increase one's chance of having seizure clusters.

UNUSUAL CASE OF STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS.

PURPOSE: To report a case of unilateral stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) in a young male showing structural changes induced by a Valsalva maneuver. METHODS: Case report of a 26-year-old oboist with SNIFR, including multimodal imaging. Eye-tracked spectral-domain optical coherence tomography (SD-OCT) was used to compare the retinal architecture at rest and during a Valsalva maneuver. RESULTS: Spectral-domain optical coherence tomography showed macular and peripapillary retinoschisis with no signs of pathologic myopia, optic pit, or vitreoretinal traction. A full-field electroretinogram showed supranormal responses in the eye studied. Magnetic resonance imaging of the brain showed no abnormalities. Eye-tracked SD-OCT scans showed an increase in retinal thickness reaching 28 microns superior to the disc during an induced Valsalva maneuver. CONCLUSION: Stellate nonhereditary idiopathic foveomacular retinoschisis is a diagnosis made when other known causes of retinoschisis have been excluded. In this patient with unilateral SNIFR, an increase in retinal thickness during a Valsalva maneuver was demonstrated. Further study would be needed to determine the mechanism producing this change and to assess its potential influence on visual prognosis.

Drug-resistant epilepsy in adults: Outcome trajectories after failure of two medications.

OBJECTIVE: To examine the seizure trajectories of adults with epilepsy developing drug-resistant epilepsy (DRE) and to identify the predictors of seizure trajectory outcome. METHODS: Adult patients failing two antiepileptic drugs (AEDs) due to inefficacy and starting their third AED at a tertiary epilepsy center were followed for seizure trajectory outcome during medical management. Seizure trajectories were categorized into one of four patterns: (1) course with constant seizures; (2) fluctuating course; (3) delayed attainment of seizure freedom (seizure freedom delayed for >12 months after start of the study, but patient stayed in seizure freedom); and (4) early attainment of seizure freedom (within 12 months of starting study). Multiple ordinal logistic regression models were used to estimate the association between trajectory categories and clinical factors. RESULTS: Four hundred three adult patients met the eligibility criteria. Of these, 212 (53%) never achieved a seizure-free period of a year or more. The trajectories of 63 patients (16%) had a complex fluctuating trajectory, 62 (15%) had delayed onset of seizure freedom, and 66 (16%) had an early seizure freedom. Independent predictors associated with more favorable outcome trajectories were epilepsy type and length of follow-up. Specifically, compared to patients with focal epilepsy of temporal lobe, patients with focal epilepsy of occipital lobe (OR 3.80, 95% confidence interval [CI] 1.00-14.51, p = 0.04), generalized genetic (OR 3.23, 95% CI 1.88-5.57, p < 0.0001), unclear epilepsy type (OR 3.82, 95% CI 1.53-9.52, p < 0.005), and both focal and generalized epilepsy(OR 11.73, 95% CI 1.69-81.34, p = 0.01) were significantly more likely to experience a better trajectory pattern. SIGNIFICANCE: Examination of patterns of seizure trajectory of patients with incident DRE showed that 31% were in continuous seizure freedom at the end of the observation period.

Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: An extended follow-up.

PURPOSE: Impact of adverse effects of antiepileptic medications (AEDs) such as cognitive side effects (CSEs) on quality of life can be significant. Here we provide an extended follow-up to our earlier study to investigate the predictors of cognitive side effects (CSEs) and relative frequency of CSEs among all commonly used AEDs. METHODS: In this retrospective study, medical records of 2860 adult outpatients with epilepsy seen at our center over a 12-year period who had taken one or more AEDs were examined. RESULTS: Of 2860 patients, 15% had intolerable CSEs attributed to at least one AED. On multiple logistic regression analysis, independent predictors of intolerable CSEs were lack of intellectual disability and polytherapy. In polytherapy, we found that intolerable CSEs were most commonly seen with topiramate (22.8% of 281 patients), significantly more than with almost all other AEDs. This was true in monotherapy as well, with significantly more intolerable CSEs occurring with topiramate (18.5% of 54 patients) than with gabapentin, carbamazepine, lamotrigine, and levetiracetam. AEDs with consistently low rates of ICSEs included gabapentin, pregabalin, lamotrigine, levetiracetam and carbamazepine. CONCLUSION: These data can help facilitate selection of AEDs.

Cross-sensitivity of patient-perceived adverse cognitive effects with antiepileptic drug use.

OBJECTIVE: The extent to which adverse cognitive effects (ACEs) to a specific antiepileptic drug (AED) affect the chance of developing ACEs to other AEDs (i.e., cross-sensitivity) is unknown. We investigated the rates of cross-sensitivity of ACEs among AEDs and examined the association between clinical characteristics and occurrence of having ACEs to multiple AEDs in adults with epilepsy. METHODS: The rates of cross-sensitivity of intolerable ACEs (IACEs; i.e., ACEs leading to dosage reduction or discontinuation) and the non-AED predictors of IACEs were investigated in 2269 patients who had taken at least two AEDs at a single center. We accounted for AED load and looked for specific cross-sensitivities between AEDs as well as cross-sensitivity based on the AED mechanism of action. RESULTS: Among the 2269 patients, the highest rates of IACEs were seen with TPM (26.3%), ZNS (9.8%), PHT (8.8%), and VPA (8.5%). Intolerable ACEs to two or more AEDs occurred in 100 patients (4.4%). History of psychiatric condition(s) and absence seizure type were independent predictors of IACEs to two or more AEDs. High rates of cross-sensitivity of IACEs were seen between phenytoin (PHT) and lamotrigine (LTG), valproate (VPA) and phenytoin, and valproate and zonisamide (ZNS). For example, of patients who had IACEs to VPA and were also prescribed ZNS, 46.2% had IACEs to ZNS (abbreviated as VPA→ZNS: 46.2%); of patients who had IACEs to ZNS and were also prescribed VPA, 37.5% had IACEs to VPA (abbreviated as ZNS→VPA: 37.5%). Other results are as follows: LTG→PHT: 28.6%, PHT→LTG: 20.0%, PHT→VPA: 42.9%, and VPA→PHT: 27.3%. No specific cross-sensitivities were found among AEDs sharing a similar mechanism of action. SIGNIFICANCE: The probability of ACE intolerability to an AED can increase if a patient developed ACE intolerability to another AED. The cross-sensitivity rates for ACE intolerability between LTG and PHT, PHT and VPA, and VPA and ZNS were found to be particularly high. The cross-sensitivity rates provided here may be clinically useful for predicting ACE intolerability in patients taking certain AEDs and for AED selection in individual patients.

Effects of two eye drop products on computer users with subjective ocular discomfort.

BACKGROUND: An increasing number of people seek medical attention for symptoms of visual discomfort due to computer vision syndrome (CVS). We compared the efficacy and adverse event rates of a new eye lubricant, OptiZen (InnoZen, Inc., polysorbate 80 0.5%) and Visine Original (Pfizer Consumer Healthcare, tetrahydrozoline HCl 0.05%). METHODS: In this double-blind parallel arm trial, 50 healthy men and women, ages 18 to 65 years, with symptoms of CVS who use a video display terminal for a minimum of 4 hours per day were randomized to OptiZen (n = 25) or Visine Original (n= 25), 1 to 2 drops b.i.d. for 5 days. The primary end-points were ocular discomfort and adverse events. RESULTS: OptiZen and Visine Original had similar efficacy in alleviating symptoms of ocular discomfort (odds ratio of 1.23 [95% confidence interval, 0.63 to 2.42], P= 0.55). OptiZen and Visine Original were very similar with respect to odds ratios and 95% confidence interval (CI) for each of the measurement times (P= 0.72). Visine Original users reported a significantly higher incidence of temporary ocular stinging/burning immediately after drug instillation (28%, 7/25) than did OptiZen users (4%, 1/24) (P= 0.05). Patients using OptiZen were 89% less likely to have stinging/burning effects than those patients using Visine Original (95% CI: 0.01 to 0.95). DISCUSSION: OptiZen and Visine Original are effective at alleviating ocular discomfort associated with prolonged computer use. Adverse event findings suggest that OptiZen causes less ocular discomfort on instillation, potentially attributable to its milder ingredient profile.