Generation and characterization of a novel Prkcd-cre rat model.

Activity of central amygdala (CeA) PKCδ expressing neurons has been linked to appetite regulation, anxiety-like behaviors, pain sensitivity, and addiction-related behaviors. Studies of the role that CeA PKCδ+ neurons play in these behaviors have largely been carried out in mice, and genetic tools that would allow selective manipulation of PKCδ+ cells in rats have been lacking. Here, we used a CRISPR/Cas9 strategy to generate a transgenic Prkcd-cre knock-in rat, and characterized this model using anatomical, electrophysiological and behavioral approaches in both sexes. In the CeA, Cre was selectively expressed in PKCδ+ cells. Anterograde projections of PKCδ+ neurons to cortical regions, subcortical regions, several hypothalamic nuclei, the amygdala complex, and midbrain dopaminergic regions were largely consistent with published mouse data. In a behavioral screen, we found no differences between Cre+ rats and Cre- wildtype littermates. Optogenetic stimulation of CeA PKCδ+ neurons in a palatable food intake assay resulted in an increased latency to first feeding and decreased total food intake, once again replicating published mouse findings. Lastly, using a real-time place preference task, we found that stimulation of PKCδ+ neurons promoted aversion, without affecting locomotor activity. Collectively, these findings establish the novel Prkcd-Cre rat line as a valuable tool, that complements available mouse lines for investigating the functional role of PKCδ+ neurons.Significance Statement The central nucleus of the amygdala (CeA), involved in processing threat and aversion signals, comprises multiple neuronal subtypes. Expression of protein kinase C isoform δ, PKCδ, marks CeA neurons that respond to aversive stimuli, and have also been shown to play a role in alcohol-related behaviors. Genetic tools to investigate the functional role of PKCδ+ neurons in rat models have been lacking. We describe the development and characterization of a novel Prkcd knock-in transgenic rat generated using CRISPR strategy. In this model, we confirm known projection targets of CeA PKCδ+ neurons and replicate functional consequences of their activation previously found in mice. This establishes the line as a novel model to study the role of PKCδ+ neurons in rat models.

Strengths and challenges in current lung cancer care: Timeliness and diagnostic procedures in six Dutch hospitals.

OBJECTIVES: Timely diagnosis of lung cancer (LC) is crucial to achieve optimal patient care and outcome. Moreover, the number of procedures required to obtain a definitive diagnosis can have a large influence on the life expectancy of a patient. Here, adherence with existing Dutch guidelines for timeliness and type and number of invasive and imaging procedures was assessed. MATERIALS AND METHODS: 1096 patients with suspected LC were enrolled in this multicenter prospective study (NL9146). The overall survival, time from referral to the first appointment with the pulmonologist, time to diagnosis and treatment, and the number of imaging and invasive procedures were evaluated. Patients were divided into different diagnostic groupsearly- and advanced stage non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), patients without LC and patients without a definitive diagnosis. RESULTS: The majority of patients (66 %) received a definitive diagnosis within 5 weeks, although the time to diagnosis of early-stage LC patients and patients without LC was significantly longer comparted to advanced stage LC. An increase in invasive procedures was seen for early-stage LC compared to advanced stage LC and for 13 % of the advanced stage non-squamous NSCLC patients up to three additional invasive procedures were performed solely to obtain sufficient material for NGS. For patients without a definitive diagnosis, 50 % did undergo at least one invasive procedure, while 11 % did not wish to undergo any invasive procedures. CONCLUSION: These insights could aid in improved LC diagnostics and efficient implementation of new techniques like liquid biopsy and artificial intelligence. This may lead to more timely LC care, a decreased number of invasive procedures, less variability between the diagnostic trajectory of different patients and aid in obtaining a definitive diagnosis for all patients.

Liquid biopsy-based decision support algorithms for diagnosis and subtyping of lung cancer.

OBJECTIVES: Pathologic subtyping of tissue biopsies is the gold standard for the diagnosis of lung cancer (LC), which could be complicated in cases of e.g. inconclusive tissue biopsies or unreachable tumors. The diagnosis of LC could be supported in a minimally invasive manner using protein tumor markers (TMs) and circulating tumor DNA (ctDNA) measured in liquid biopsies (LBx). This study evaluates the performance of LBx-based decision-support algorithms for the diagnosis of LC and subtyping into small- and non-small-cell lung cancer (SCLC and NSCLC) aiming to directly impact clinical practice. MATERIALS AND METHODS: In this multicenter prospective study (NL9146), eight protein TMs (CA125, CA15.3, CEA, CYFRA 21-1, HE4, NSE, proGRP and SCCA) and ctDNA mutations in EGFR, KRAS and BRAF were analyzed in blood of 1096 patients suspected of LC. The performance of individual and combined TMs to identify LC, NSCLC or SCLC was established by evaluating logistic regression models at pre-specified positive predictive values (PPV) of ≥95% or ≥98%. The most informative protein TMs included in the multi-parametric models were selected by recursive feature elimination. RESULTS: Single TMs could identify LC, NSCLC and SCLC patients with 46%, 25% and 40% sensitivity, respectively, at pre-specified PPVs. Multi-parametric models combining TMs and ctDNA significantly improved sensitivities to 65%, 67% and 50%, respectively. CONCLUSION: In patients suspected of LC, the LBx-based decision-support algorithms allowed identification of about two-thirds of all LC and NSCLC patients and half of SCLC patients. These models therefore show clinical value and may support LC diagnostics, especially in patients for whom pathologic subtyping is impossible or incomplete.

Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer.

Identification of actionable mutations in advanced stage non-squamous non-small-cell lung cancer (NSCLC) patients is recommended by guidelines as it enables treatment with targeted therapies. In current practice, mutations are identified by next-generation sequencing of tumor DNA (tDNA-NGS), which requires tissue biopsies of sufficient quality. Alternatively, circulating tumor DNA (ctDNA) could be used for mutation analysis. This prospective, multicenter study establishes the diagnostic value of ctDNA analysis by droplet digital PCR (ctDNA-ddPCR) in patients with primary lung cancer. CtDNA from 458 primary lung cancer patients was analyzed using a panel of multiplex ddPCRs for EGFR (Ex19Del, G719S, L858R, L861Q and S768I), KRAS G12/G13 and BRAF V600 mutations. For 142 of 175 advanced stage non-squamous NSCLC patients tDNA-NGS results were available to compare to ctDNA-ddPCR. tDNA-NGS identified 98 mutations, of which ctDNA-ddPCR found 53 mutations (54%), including 32 of 45 (71%) targetable driver mutations. In 2 of these 142 patients, a mutation was found by ctDNA-ddPCR only. In 33 advanced stage patients lacking tDNA-NGS results, ctDNA-ddPCR detected 15 additional mutations, of which 7 targetable. Overall, ctDNA-ddPCR detected 70 mutations and tDNA-NGS 98 mutations in 175 advanced NSCLC patients. Using an up-front ctDNA-ddPCR strategy, followed by tDNA-NGS only if ctDNA-ddPCR analysis is negative, increases the number of mutations found from 98 to 115 (17%). At the same time, up-front ctDNA-ddPCR reduces tDNA-NGS analyses by 40%, decreasing the need to perform (additional) biopsies.

Extinction of Cocaine Memory Depends on a Feed-Forward Inhibition Circuit Within the Medial Prefrontal Cortex.

BACKGROUND: Cocaine-associated environments (i.e., contexts) evoke persistent memories of cocaine reward and thereby contribute to the maintenance of addictive behavior in cocaine users. From a therapeutic perspective, enhancing inhibitory control over cocaine-conditioned responses is of pivotal importance but requires a more detailed understanding of the neural circuitry that can suppress context-evoked cocaine memories, e.g., through extinction learning. The ventral medial prefrontal cortex (vmPFC) and dorsal medial prefrontal cortex (dmPFC) are thought to bidirectionally regulate responding to cocaine cues through their projections to other brain regions. However, whether these mPFC subregions interact to enable adaptive responding to cocaine-associated contextual stimuli has remained elusive. METHODS: We used antero- and retrograde tracing combined with chemogenetic intervention to examine the role of vmPFC-to-dmPFC projections in extinction of cocaine-induced place preference in mice. In addition, electrophysiological recordings and optogenetics were used to determine whether parvalbumin-expressing inhibitory interneurons and pyramidal neurons in the dmPFC are innervated by vmPFC projections. RESULTS: We found that vmPFC-to-dmPFC projecting neurons are activated during unreinforced re-exposure to a cocaine-associated context, and selective suppression of these cells impairs extinction learning. Parvalbumin-expressing inhibitory interneurons in the dmPFC receive stronger monosynaptic excitatory input from vmPFC projections than local dmPFC pyramidal neurons, consequently resulting in disynaptic inhibition of pyramidal neurons. In line with this, we show that chemogenetic suppression of dmPFC parvalbumin-expressing inhibitory interneurons impairs extinction learning. CONCLUSIONS: Our data reveal that vmPFC projections mediate extinction of a cocaine-associated contextual memory through recruitment of feed-forward inhibition in the dmPFC, thereby providing a novel neuronal substrate that promotes extinction-induced inhibitory control.

A neural substrate of compulsive alcohol use.

Alcohol intake remains controlled in a majority of users but becomes "compulsive," i.e., continues despite adverse consequences, in a minority who develop alcohol addiction. Here, using a footshock-punished alcohol self-administration procedure, we screened a large population of outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration. Using unsupervised clustering, we found that this behavior emerged as a stable trait in a subpopulation of rats and was associated with activity of a brain network that included central nucleus of the amygdala (CeA). Activity of PKCδ+ inhibitory neurons in the lateral subdivision of CeA (CeL) accounted for ~75% of variance in punishment-resistant alcohol taking. Activity-dependent tagging, followed by chemogenetic inhibition of neurons activated during punishment-resistant self-administration, suppressed alcohol taking, as did a virally mediated shRNA knockdown of PKCδ in CeA. These findings identify a previously unknown mechanism for a core element of alcohol addiction and point to a novel candidate therapeutic target.

A Synaptic Framework for the Persistence of Memory Engrams.

The ability to store and retrieve learned information over prolonged periods of time is an essential and intriguing property of the brain. Insight into the neurobiological mechanisms that underlie memory consolidation is of utmost importance for our understanding of memory persistence and how this is affected in memory disorders. Recent evidence indicates that a given memory is encoded by sparsely distributed neurons that become highly activated during learning, so-called engram cells. Research by us and others confirms the persistent nature of cortical engram cells by showing that these neurons are required for memory expression up to at least 1 month after they were activated during learning. Strengthened synaptic connectivity between engram cells is thought to ensure reactivation of the engram cell network during retrieval. However, given the continuous integration of new information into existing neuronal circuits and the relatively rapid turnover rate of synaptic proteins, it is unclear whether a lasting learning-induced increase in synaptic connectivity is mediated by stable synapses or by continuous dynamic turnover of synapses of the engram cell network. Here, we first discuss evidence for the persistence of engram cells and memory-relevant adaptations in synaptic plasticity, and then propose models of synaptic adaptations and molecular mechanisms that may support memory persistence through the maintenance of enhanced synaptic connectivity within an engram cell network.

Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer.

Neuron-specific enolase (NSE) is a well-known biomarker for the diagnosis, prognosis and treatment monitoring of small-cell lung cancer (SCLC). Nevertheless, its clinical applicability is limited since serum NSE levels are influenced by hemolysis, leading to falsely elevated results. Therefore, this study aimed to develop a hemolysis correction equation and evaluate its role in SCLC diagnostics. Two serum pools were spiked with increasing amounts of hemolysate obtained from multiple individuals. A hemolysis correction equation was obtained by analyzing the relationship between the measured NSE concentration and the degree of hemolysis. The equation was validated using intentionally hemolyzed serum samples, which showed that the correction was accurate for samples with an H-index up to 30 µmol/L. Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results. Therefore, a hemolysis correction equation should be used to correct falsely elevated NSE concentrations. Results of samples with an H-index above 30 µmol/L should not be reported to clinicians. Application of the equation illustrates the importance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.

A persistent alcohol cue memory trace drives relapse to alcohol seeking after prolonged abstinence.

Alcohol use disorder is characterized by a high risk of relapse during periods of abstinence. Relapse is often triggered by retrieval of persistent alcohol memories upon exposure to alcohol-associated environmental cues, but little is known about the neuronal circuitry that supports the long-term storage of alcohol cue associations. We found that a small ensemble of neurons in the medial prefrontal cortex (mPFC) of mice was activated during cue-paired alcohol self-administration (SA) and that selective suppression of these neurons 1 month later attenuated cue-induced relapse to alcohol seeking. Inhibition of alcohol seeking was specific to these neurons as suppression of a non-alcohol-related or sucrose SA-activated mPFC ensemble did not affect relapse behavior. Hence, the mPFC neuronal ensemble activated during cue-paired alcohol consumption functions as a lasting memory trace that mediates cue-evoked relapse long after cessation of alcohol intake, thereby providing a potential target for treatment of alcohol relapse vulnerability.

Memory strength gates the involvement of a CREB-dependent cortical fear engram in remote memory.

Encoding and retrieval of contextual memories is initially mediated by sparsely activated neurons, so-called engram cells, in the hippocampus. Subsequent memory persistence is thought to depend on network-wide changes involving progressive contribution of cortical regions, a process referred to as systems consolidation. Using a viral-based TRAP (targeted recombination in activated populations) approach, we studied whether consolidation of contextual fear memory by neurons in the medial prefrontal cortex (mPFC) is modulated by memory strength and CREB function. We demonstrate that activity of a small subset of mPFC neurons is sufficient and necessary for remote memory expression, but their involvement depends on the strength of conditioning. Furthermore, selective disruption of CREB function in mPFC engram cells after mild conditioning impairs remote memory expression. Together, our data demonstrate that memory consolidation by mPFC engram cells requires CREB-mediated transcription, with the functionality of this network hub being gated by memory strength.

Clinical Performance of a New Bitangential Mini-scleral Lens.

SIGNIFICANCE: New bitangential mini-scleral lens designs provide a highly precise fit, follow the scleral shape, are comfortable to wear, and can correct residual astigmatism. This new scleral lens design complements the arsenal of medical contact lenses available to eye care practitioners. PURPOSE: The aim of this study was to evaluate the subjective and objective performance of a new mini-scleral lens design with a bitangential periphery. METHODS: In this observational study, data were collected for up to 15 months (median, 84 days; interquartile range, 76 days) from the left eyes of 133 patients fitted with this newly designed lens. Data were recorded during regular visits at Visser Contact Lens Practice's scleral lens clinics: diagnosis, clinical indication for scleral lenses, previous contact lens type, subjective performance, horizontal visible iris diameter, corrected distance visual acuity, and scleral lens fitting characteristics. RESULTS: The most common indication was keratoconus (45%), followed by irregular astigmatism (22%), keratoplasty (16.5%), ocular surface disease (13.5%), and other forms of irregular astigmatism (3%). The majority of patients (79%) scored comfort as either a 4 or 5 (out of 5), and 82% wore their lenses 12 hours or longer a day. Most lenses (81%) had a diameter of 16 mm (median, 16 mm; range, 15.5 to 17 mm) and were composed of Boston XO2 (46%), Menicon Z (44%), Boston XO (9%), or Boston Equalens II (1%). The median corrected distance visual acuity was 0.022 logarithm of the minimal angle of resolution (interquartile range, 0.155). The fitting characteristics revealed optimal values for centration and movement in 91% and 83%, respectively. Finally, the median stabilization axis was 50 degrees. CONCLUSIONS: New mini-scleral lenses with bitangential peripheral geometry yield satisfactory clinical results and good subjective performance and are therefore an effective option for managing patients who have irregular astigmatism or other corneal pathology.

Objective and subjective evaluation of the performance of medical contact lenses fitted using a contact lens selection algorithm.

PURPOSE: To evaluate the performance of medical contact lenses (CLs) for a wide range of clinical indications. DESIGN: Prospective cross-sectional study. METHODS: A total of 281 eyes were evaluated in 281 consecutive patients (≥18 years of age; CL use ≥3 months) who visited the contact lens service in a tertiary academic clinic for a scheduled follow-up visit. The main outcome measured were clinical indications for CL wear; CL type; change in corrected distance visual acuity (CDVA) with CL use; CL wearing duration; CL wearing time; subjective performance measured using a visual analog scale (VAS) questionnaire (score range: 0-100); and effectiveness of the lens-selection algorithm. RESULTS: Wearing CLs significantly improved CDVA compared to wearing spectacles (median change: -0.15 logMAR, range: 1.00 to -2.10; P<.001). Daily-wear CLs were worn by 77% of patients for a median of 15h/day (range: 5-18h/day), median 7 days/week (range: 1-7 days/week). High subjective scores were measured, with similar results obtained between the scleral lens and soft lens groups. The medical CL fitting was found to be generally effective (the overall satisfaction rating was ≥70 for 81% of patients). CONCLUSIONS: Fitting CLs based on the lens-selection algorithm yielded positive clinical results, including improved visual acuity, satisfactory wearing time, and high overall subjective performance. Moreover, subjective performance was similar between users of scleral lenses and users of soft lenses. These results underscore the importance of prescribing scleral lenses and the need for tertiary eye clinics to offer patients a variety of CL types.

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference.

Cocaine-associated environmental cues sustain relapse vulnerability by reactivating long-lasting memories of cocaine reward. During periods of abstinence, responding to cocaine cues can time-dependently intensify a phenomenon referred to as 'incubation of cocaine craving'. Here, we investigated the role of the extracellular matrix protein brevican in recent (1 day after training) and remote (3 weeks after training) expression of cocaine conditioned place preference (CPP). Wild-type and Brevican heterozygous knock-out mice, which express brevican at ~50% of wild-type levels, received three cocaine-context pairings using a relatively low dose of cocaine (5 mg/kg). In a drug-free CPP test, heterozygous mice showed enhanced preference for the cocaine-associated context at the remote time point compared with the recent time point. This progressive increase was not observed in wild-type mice and it did not generalize to contextual-fear memory. Virally mediated overexpression of brevican levels in the hippocampus, but not medial prefrontal cortex, of heterozygous mice prevented the progressive increase in cocaine CPP, but only when overexpression was induced before conditioning. Post-conditioning overexpression of brevican did not affect remote cocaine CPP, suggesting that brevican limited the increase in remote CPP by altering neuro-adaptive mechanisms during cocaine conditioning. We provide causal evidence that hippocampal brevican levels control time-dependent enhancement of cocaine CPP during abstinence, pointing to a novel substrate that regulates incubation of responding to cocaine-associated cues.

Scleral lens influence on corneal curvature and pachymetry in keratoconus patients.

OBJECTIVES: To investigate the influence of full scleral lenses on corneal curvature and pachymetry in keratoconus patients. METHODS: In this intervention study, 20 eyes of 14 patients were measured by Scheimpflug imaging (Pentacam HR, Oculus) at two time points: directly and ≥1 week after scleral lens removal. Steep, flat and maximal keratometry (K(steep), K(flat) and K(max)) and optical pachymetry were analyzed. A generalized estimating equation analysis was performed to correct for paired eyes. RESULTS: Directly after scleral lens removal, all three curvature parameters were significantly flatter compared to ≥1 week after scleral lens removal. Average K(steep) was 0.7 diopter (D) lower (P<0.001), average K(flat) was 0.5D lower (P=0.037) and average K(max) was 1.1D lower (P<0.001). Directly after scleral lens removal, average optical pachymetry was ±2.5% higher (P<0.001) compared to ≥1 week after scleral lens removal. CONCLUSIONS: Although scleral lenses do not mechanically touch the cornea, curvature and pachymetry seem to be influenced by scleral lens wear in keratoconus patients. The duration of these changes remain unclear.

Scleral lens tolerance after corneal cross-linking for keratoconus.

PURPOSE: Subjective and objective evaluation of scleral lens tolerance and fitting before and after corneal cross-linking (CXL) for progressive keratoconus. METHODS: In this prospective cohort, evaluations were made of 18 unilateral eyes in patients who underwent CXL and had been wearing scleral lenses before the procedure. All the patients gave informed consent; they were able to cooperate with the study, were eligible for CXL, had been wearing well-fitting scleral lenses for at least 3 months, and had no other active ocular disease. Data were collected before and 1 year after CXL. Outcome measures were changes in clinical and subjective scleral lens performance. The following components were studied: scleral lens corrected distance visual acuity, scleral lens specifications, scleral lens fit, wearing time, and subjective measures on visual analogue scale questionnaires (1 to 100 mm). RESULTS: There was no significant change in scleral lens corrected distance visual acuity (p = 0.632). Sixty-one percent of eyes needed a scleral lens fit and/or power change. Wearing time (median, 16 hours per day) and subjective tolerance were found to be stable. CONCLUSIONS: Scleral lens tolerance after CXL appeared to be stable.

Medical applications and outcomes of bitangential scleral lenses.

PURPOSE: To evaluate the clinical results of a new scleral lens design with a bitangential (nonrotationally symmetrical) periphery. METHODS: All the necessary data were obtained during the 1-year study period. The bitangential scleral lenses were fitted and monitored according to a standardized fitting methodology. They were cut by precise submicron lathing from high-oxygen-permeable materials (including 10 scleral lenses from Menicon Z material). Subjective performance, visual acuity, and scleral lens-fitting characteristics were recorded after a median of 9.4 weeks (range, 3 weeks to 1 year). RESULTS: Diagnoses in the 213 eyes (in 144 patients) were keratoconus (n = 121 eyes; 56.8%), ocular surface diseases (n = 31 eyes; 14.6%), penetrating keratoplasty (n = 29 eyes; 13.6%), and other forms of irregular astigmatism (n = 28 eyes; 13.1%). Many patients (164 lenses; 77.0%) gave high ratings for comfort. The most common diameter was 20.0 mm (162 lenses; 76.1%) (range, 18.5 to 21.5 mm). Median decimal best-corrected visual acuity with the bitangential scleral lenses was 0.8 (equivalent to Snellen 20/25) (range, 0 to 1.5). Most bitangential scleral lenses showed good fitting characteristics: optimal values were seen for lens movement (208 lenses; 97.7%) and lens position (208 lenses; 97.7%). Median central corneal clearance was 0.2 mm; clearances differed in the four peripheral directions. The median stabilization axis was 140 degrees (range, 0 to 180 degrees) in the right eyes and 60 degrees (range, 0 to 180 degrees) in the left eyes. CONCLUSIONS: The bitangential scleral lens-fitting and performance characteristics were clear and effective for the health professional and the patient. The high-oxygen-permeable material Menicon Z may, in theory, be of benefit to corneas with a high oxygen demand.

Modern scleral lenses part I: clinical features.

PURPOSE: To evaluate the indications for modern scleral lenses and their clinical performance in patients who were fitted with scleral lenses at the authors' practices. METHODS: In this cross-sectional survey, all the necessary data were obtained at the first follow-up visit during the 5-month study period. There were four types of scleral lenses: spherical, front-surface toric, back-surface toric, and bitoric. The preformed scleral lens fitting technique developed at Visser Contact Lens Practice was used in all patients. The lenses were cut by precise Sub Micron Lathing from a Boston Equalens II blank at Procornea. Visual acuity and slitlamp findings were recorded. A specially designed classification for scleral lens fitting was used to investigate clinical performance. RESULTS: The largest proportion of the 178 patients (284 eyes) were diagnosed with keratoconus (143 [50.4%] eyes) followed by postpenetrating keratoplasty (56 [19.7%] eyes). The remaining diagnoses were irregular astigmatism, keratitis sicca, corneal dystrophy, and multiple diagnoses. The ratio of spherical to back-surface toric designs was 1:1.1. Clinical examination showed sharp increases in visual acuity (median increase, 0.45) and safe physiologic responses of the anterior eye. All the patients could continue to wear scleral lenses, with 79.2% with the same lens parameters. CONCLUSIONS: Several types of corneal abnormality were managed successfully with modern scleral lenses. The main indication was optical correction of an irregular corneal surface. Satisfactory clinical performance meant that all the patients could continue to wear their scleral lenses.

Modern scleral lenses part II: patient satisfaction.

PURPOSE: To evaluate the subjective performance of modern scleral lenses in patients of the clinics of Visser Contact Lens Practice. METHODS: In this cross-sectional survey, all the necessary data were collected at the first follow-up visit during the 5-month study period. In accordance with the preformed fitting technique developed at Visser Contact Lens Practice, four types of scleral lenses were used: spherical, front-surface toric, back-surface toric, and bitoric. Subjective performance was investigated during an interview that included the use of a five-point Likert scale and by means of a questionnaire supplemented by a 100-mm visual analog scale (VAS). RESULTS: The interview and questionnaire showed high scores for patient satisfaction with the current scleral lens in the 178 patients (284 eyes) (median score, 4; range Likert scale, 1-5; median score, >or=75; range VAS, 1-100). Significant increases in scores were seen with the current scleral lens compared to the former correction: 78.9% for comfort, 78.2% for visual quality, and 87.7% for overall satisfaction (n=284 eyes) (P<0.001). In the 99 eyes that switched from back-surface spherical to back-surface toric designs, the following significant increases were seen: 61.6%, 37.4%, and 65.7%, respectively (P<0.001). CONCLUSIONS.: High patient satisfaction was seen with all the modern scleral lens designs in the management of several forms of corneal abnormality. The interview showed differences in comfort, visual quality, and overall satisfaction in favor of the back-surface toric designs compared to the back-surface spherical designs.

Advantages of toric scleral lenses.

PURPOSE: The purpose of this study was to investigate whether back surface toric scleral lenses stabilized (i.e., returned to their original position after rotation) and how long the return times were. Return time was studied in relation with actual wearing time and comfort; moreover, the performance of the spherical scleral lens was compared with the toric scleral lens design. METHODS: Toric scleral lenses were rotated clockwise and counterclockwise over 60 degrees. Return times and the actual wearing time were recorded. Results were transformed into nasal and temporal return times for symmetry reasons. The present and former types of correction were compared for comfort (ranging from 0: very poor to 10: excellent) and regular wearing time. All the subjects attended regular follow-up visits. RESULTS: Forty-three subjects (43 lenses) entered the study. All the lenses returned to the original position within a median of 4 seconds after nasal rotation and 6 seconds after temporal rotation. A significant correlation was found between mean return times and actual wearing time (r = 0.63). Significant increases in median comfort (from 6-8) and median wearing time (from 15-16 hours) were demonstrated when the toric scleral lens designs were compared with the former type of correction (both p < 0.001). Median comfort and median wearing time also increased significantly after changing from spherical scleral lenses to the toric design (from 7-8 and from 14-16 hours, both p < 0.001, n = 27 eyes). CONCLUSIONS: Toric scleral lenses returned rapidly to their original position after rotation. The flattest meridian of the toric scleral lenses stabilized symmetrically. Patient interviews demonstrated differences in comfort and wearing time in favor of the toric design.