Dual-Acting Zeta-Potential-Changing Micelles for Optimal Mucus Diffusion and Enhanced Cellular Uptake after Oral Delivery.

CONTEXT: Overcoming the intestinal mucosal barrier can be a challenge in drug delivery. Nanoemulsions with negative zeta potentials can effectively permeate the mucus layer, but those with positive zeta potentials are better taken up by cells; a nanoemulsion with capricious zeta potential from negative to positive can achieve both good permeation and high uptake. OBJECTIVE: This study aimed to develop dual-acting zeta-potential-amphoteric micelles enabling optimal muco-permeation and enhancement of cellular uptake. METHODS: A micellar pre-concentrate was prepared from 15% Labrasol, 15% Kolliphor EL, 30% Kolliphor RH 40, and 40% dimethylsulfoxide. The micellar pre-concentrate was loaded with anionic stearic acid (SA), forming ionic complexes with cationic polymers at a ratio of 25:1 with Eudragit RS 100 and Eudragit RL 100. Blank micelles and those containing complexes were separately diluted in physiological buffers and examined for their droplet sizes, polydispersity indices (PDIs), zeta potentials, and cytotoxicity. The SA release from the micellar complexes was evaluated in 0.1 mM phosphate buffer (pH 6.8) containing 0.001% fluorescein, thereby enabling an instant decrease in fluorescence. Finally, the micelles were loaded with the model drug fluorescein diacetate (FDA) and evaluated for their muco-permeation behavior and cellular uptake. RESULTS: The micellar dilutions formed micelles at the critical micelle concentration (CMC) of 312 µg/mL and showed a uniform average droplet size of 14.2 nm, with a PDI < 0.1. Micellar dilutions were non-cytotoxic when used at 1:100 in a physiological medium. Micelles loaded with ionic complexes achieved a sustained release of 95.5 ± 3.7% of the SA in 180 min. Moreover, the zeta potential of the complex-loaded micelles shifted from -5.4 to +1.8 mV, whereas the blank micelles showed a stabilized zeta potential of -10 mV. Furthermore, the negatively charged blank and complex-loaded micelles exhibited comparable muco-permeation, with an overall average of 58.2 ± 3.7% diffusion of FDA. The complex-loaded micellar droplets, however, provided a significantly higher cellular uptake of the model drug FDA (2.2-fold, p ≤ 0.01) Conclusion: Due to undergoing a shift in zeta potential, the modified micelles significantly enhanced cellular uptake while preserving mucus-permeating properties.

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro.

The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 1:1, 2:1, and 4:1 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5'-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB forming a yellow dye. The droplet size of SEDDS FA and SEDDS FB were in the range of 100 ± 20 nm and 40 ± 10 nm, respectively, with a PDI < 0.5. The zeta potential of SEDDS FA and SEDDS FB increased after the incorporation of complexes. Cell viability remained above 80% after incubation with SEDDS FA and SEDDS FB in a concentration of 1% and 3% for 4 h. Without any polymer, CTL was entirely released from both SEDDS within seconds. In contrast, the higher the cationic lipophilic polymer to CTL ratio in SEDDS, the more sustained was the release of CTL. Among the polymers which were evaluated, Eudragit RL provided the most sustained release. SEDDS FA containing Eudragit RL and CTL in a ratio of 1:1 released 64.78 ± 8.28% of CTL, whereas SEDDS FB containing the same complex showed a release of 91.85 ± 1.17% within 1 h. Due to the formation of lipophilic ionic polymer complexes a sustained drug release from oily droplets formed by SEDDS can be achieved. Taking into account that drugs are otherwise instantly released from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.

A comparison of selected physico-chemical properties of calcium alginate fibers produced using two different types of sodium alginate.

Sodium alginate is a non-toxic natural polysaccharide found in marine brown algae. It is able to form solid gels by the action of poly-valent cations (commonly calcium but not magnesium) which cross-link the polysaccharide chains at the guluronic acid groups. Alginate-based products are popular in many industries, including food production and in pharmaceutical and biomedical applications. It is utilized in manufacture of wound-care products due to its biocompatibility and gel forming capabilities upon the absorption of wound exudate. Considering the potential influence of the alginate composition on the properties of the resultant fibers, two sodium alginate powders were selected based on their contrasting compositions. The GHB alginate was high in guluronic acid whereas the LKX alginate was high in mannuronic acid. The sodium alginate solutions (4% w/w) were extruded into a calcium chloride (3% w/v) bath to produce calcium alginate fibers. The fibers were dried at 22 °C and 32% relative humidity for 72 h. Selected properties of the blank (unloaded) fibers were analysed: diameter measurements by optical microscopy, mechanical strength using a universal testing machine, morphology by scanning electron microscopy, and calcium content by inductively coupled plasma atomic emission spectroscopy. One of the key aims of this work was to evaluate the variability of these properties along moderately large lengths of fiber and to determine the difference (if any) between replicate lengths of fibers. This study showed that the alginate type influenced selected properties of the resultant fibers. The mean diameter and calcium content of the GHB fibers were 232 µm and 2.79µmoles/mg respectively, whereas the LKX fibers were about 10% thicker and had 2.58µmoles/mg calcium ion content. The fibers of each alginate could be distinguished visually based on gross differences as well as differences in their microstructure. Mechanical testing of the fibers produced stress-strain plots displaying largely non-elastic behaviour. There was no statistically significant (p < 0.05) difference between the Young's modulus or the strain at break for the two types of fibers, namely about 5-5.6 GPa and 0.123-0.131 respectively. All the measured properties were found to be consistent along the nine sampling positions along the lengths of fibers and were reproducible between the different batches of fibers.

Extended compatibility of fentanyl and ketamine in dextrose 5.

BACKGROUND: There are no published studies that report on fentanyl and ketamine compatibility in dextrose 5% solution as commonly practiced in hospital settings. METHODS: This study assessed the compatibility of fentanyl and ketamine after their reconstitution in dextrose 5% under ambient temperature and humidity conditions in a hospital setting. Each sample of fentanyl and ketamine was prepared in triplicate by adding dextrose 5% to a prefilled syringe until final concentrations of 9.8 µg mL-1 for fentanyl and 192 µg mL-1 for ketamine were achieved. The solutions were stored in syringes at an ambient temperature ranging 26-28°C either under a mixture of daylight and ambient lighting. A sample was taken from the syringes at the following times: 0, 8, 24, 72, 120, and 168 hours. The samples from each solution were checked for physical changes, pH and their concentration assessed by high-performance liquid chromatography. RESULTS: The solutions were clear and no physical changes were seen. The pH of fentanyl and ketamine decreased dramatically after 72 hours. The concentrations of fentanyl remained 90-110% only for 24 hours, while ketamine remained 90-110% for 168 hours. CONCLUSION: Solutions of fentanyl and ketamine in dextrose 5% may be used in prefilled syringes only up to 24 hours and 72 hours after reconstitution, respectively.

Elective surgical outcomes of patients in Christchurch, New Zealand.

AIM: Most studies assessing mortality after surgery have been undertaken in major public hospitals or are procedure specific. The aim of this study was to determine mortality after elective surgery at a total community level with inclusion of all patients undergoing elective surgery. METHOD: This was a prospective study of all patients that underwent elective surgery in Christchurch, New Zealand, within a calendar month. For each patient, we collected demographic data, American Society of Anaesthesiologists physical status classification (ASA), type of anaesthetic and surgical specialty. The primary outcome was 30-day mortality and the secondary outcome was 90-day mortality. RESULTS: Four thousand seven hundred and fifteen patients were included in this study. Two thousand five hundred and seventy-eight (55%) were female and the median age was 56 years (range 0-99 years). Three thousand one hundred and forty-two (67%) patients had a general anaesthetic. By day 30, 11 (0.2%) patients had died and by day 90, 27 (0.6%) patients had died. Of the 27 deaths within 90 days after surgery, one was possibly anaesthesia-related (0.02%), while the majority were due to progression of disease (18). CONCLUSION: This study shows a lower mortality than what has previously been reported for elective surgical procedures when the denominator is the total community number of operations.

In vitro analysis of the effect of in-line 1.2 micron filters on two formulations of propofol (2,6-diisopropyl phenol).

Recent evidence has shown improved outcomes in pediatric intensive care units with the intensive use of intravenous in-line filtration. This has caused resurgence in interest in filter use but has raised questions in relation to emulsion-based formulations such as propofol. Our objective was to test two propofol products, Diprivan(®) and Fresofol(®), with the Pall Lipipor(®) TNA and Lipipor NLF intravenous in-line filters and to assay the content before and after filtration under typical infusion conditions. The propofol emulsions were delivered from a 50 mL syringe through an extension set and into either a Lipipor TNA (50 mL/h(-1)) or Lipipor NLF (20 mL/h(-1)) filter. Samples were taken at regular intervals and assayed using a high-performance liquid chromatography method before and after filtration. No evidence was found of a significant concentration change during passage of either product through either model of filter. Propofol from two products was found to pass through two different types of Pall 1.2 µm intravenous in-line filters. There was no significant change in concentration before and after filtration under typical conditions of administration. In conclusion, administration of these products through these models of in-line filter would be safe and effective.

Comparison of selected physico-chemical properties of calcium alginate films prepared by two different methods.

Sodium alginate (SA) is a naturally occurring, non-toxic, polysaccharide that is able to form gels after exposure to calcium. These gels have been used in food and biomedical industries. This is the first direct comparison of two different methods of calcium alginate film production, namely interfacial gelation (IFG) and dry cast gelation (DCG). IFG films were significantly thicker than DCG films, and were more extensively rehydrated in water and 0.1M HCl than the DCG films. During rehydration in 0.1M HCl almost all calcium ions were lost. Under scanning electron microscopy, IFG films appeared less dense than DCG films. IFG films were mechanically weaker than DCG films, and both types of film were weaker after rehydration in 0.1M HCl compared with deionized water. Permeation of theophylline (TPL) was evaluated in-vitro; the diffusion coefficient (D) of the TPL was almost 90 times lower in DCG films than IFG films when both were rehydrated in water. Although the 0.1M HCl rendered both gels more permeable to TPL, D of TPL was still about five times lower in DCG compared to IFG films. The evaluation of selected physico-chemical properties of films is important, since this information may inform the choice of gelation technique used to produce calcium alginate coatings on pharmaceutical products.

Sevoflurane end-tidal to effect-site equilibration in women determined by response to laryngeal mask airway insertion.

BACKGROUND: End-tidal concentrations (CET) have been used to guide delivery of inhaled anesthetic drugs for many years. Effect-site concentrations (Ceff) are a frequently used guide to therapy with IV drugs and should also be of benefit with inhaled drugs, especially during periods of rapid change. For Ceff to be useful, the appropriate levels required for any given end point, and the delay between central compartment and effect, need to be defined. In this study, we explored these relationships for the effect of response to insertion of the classic laryngeal mask airway (cLMA) and compared the utility of CET and Ceff-guided cLMA insertion. METHOD: We studied 30 ASA physical status I or II patients in whom induction with sevoflurane alone and use of the cLMA were appropriate. After oxygen administration from a circle system with a total gas flow of 6 L/min, the sevoflurane vaporizer dial was set to 6%. cLMA insertion was attempted at a predetermined Ceff calculated in real time based on measured CET. Target levels were chosen using up-and-down methodology. The initial value was 2.5 vol% with a step size of 0.2 vol%. Subjects showing a gross motor response were responders, and the target was increased for the next subject. Those without such a response were nonresponders, and the target was decreased for the next subject. Data collection continued until after 7 transitions from nonresponder to responder. For each subject, after the first transition, we calculated a Ceff time series from the measured CET time series for 11 t(1/2)ke0 values between 0.5 and 5.0 minutes. We combined data from 2 studies of equilibrium 50% effective concentration (EC50) for LMA insertion to derive a pooled EC50 of 2.17%. We determined graphically the t(1/2)ke0 that gave a mean EC50 of 2.17% in our subjects. We constructed receiver operator characteristic curves to compare the utility of CET and Ceff-guided cLMA insertion. RESULTS: The 30 patients studied were all women, ASA physical status I or II, aged between 22 and 66 years (mean 38). Consciousness was lost after 99.2 (SD 11.1) seconds, and the target for cLMA insertion reached after 256 (57) seconds. The optimum t(1/2)ke0 was 2.25 minutes (95% confidence interval, 2.0-2.5 minutes). The area under the receiver operator characteristic curves was significantly different at 0.87 (SE 0.06) for Ceff and 0.63 (0.11) for CET. CONCLUSIONS: This study confirmed that real-time calculation and display of Ceff based on measured CET values are feasible. We determined the optimum t(1/2)ke0 for sevoflurane for the effect of cLMA insertion as 2.25 minutes, similar to that determined for loss of consciousness using the raw electroencephalogram. We also showed that Ceff is a more reliable (P < 0.05) guide to successful cLMA insertion than CET.

Factors affecting the production of nanostructure lipid carriers of valproic acid.

The objective of this study was to optimize a nano-lipid carrier (NLCs) of valproic acid for nasal delivery using statistical methods. NLCs were prepared by solvent diffusion method followed by ultrasonication. After a preliminary screening study using Taguchi design, the Box-Behnken statistical model using desirability function was applied to evaluate variables affecting key specifications (minimum particle size, maximum drug loading and optimum release) of nano-lipid carriers of valproic acid. Each variable was assessed at three levels of surfactant concentration, acetone/ethanol volume ratio and organic/aqueous phase volume ratio. The best predicted model for particle size and drug release was quadratic model, while for drug loading, 2 factor interaction model fitted better. The measured results for the optimized formulation were a mean size of 154 nm, 47% payload and 75% of drug content released within 21 days. The optimum formulation was obtained using 1% of Poloxamer-188 as surfactant, organic/aqueous phase volume ratio of 1/5 and acetone/ethanol volume ratio of 3/1. Overall, the results show that entrapment of valproic acid in nano-lipid carriers was achieved. Such carriers might be a promising delivery system in the treatment of seizures via the nasal route of administration.

Swelling and diffusion studies of calcium polysaccharide gels intended for film coating.

The aim of this paper was to study the swelling and diffusion behaviors of calcium polysaccharide gel (CaPG) films prepared by an interfacial complexation technique, a new gel formation method that allowed calcium ions to diffuse from a source to form gel films with polysaccharide (i.e., alginate or pectin). The dynamic swelling behavior of CaPG films showed that swelling was a function of time. Most CaPG films showed a maximum amount of water absorption during the first few hours. The films swelled less in water and acidic media but extensively swelled in 0.1M NaCl. The rehydration of the dry films in the acidic media or the 0.1M NaCl solution also lead to the extraction of most of the calcium ions from the CaPG within 4h or less. Partitioning and diffusion of a model drug, theophylline (TPL), were measured through CaPG films equilibrated in different media. The partition and diffusion coefficients of TPL through CaPG films were found to vary, depending upon polysaccharide type, concentration and equilibration medium. The results suggest that both partition and pore mechanisms operated concurrently in the transport of TPL through CaPG films equilibrated in different media.

Development of polysaccharide gel-coated pellets for oral administration: swelling and release behavior of calcium pectinate gel.

The aim of this study was to examine the effect of pellet size, pectin type, pectin concentration, and dissolution medium on the swelling and drug release behavior of spherical pellets containing theophylline and coated with 2 different calcium pectinates, using a multi-level factorial design approach. The spherical pellets were prepared by an extrusion-spheronization method and then coated with calcium pectinate using the diffusion-controlled interfacial complexation technique, which provides a defect-free and uniform coating on solid cores. Theophylline release from the pellets was slowed by the application of the coatings. The time to release 50% of the payload (ie, T50) in an acidic medium was approximately 7 minutes from uncoated small pellets and was 55 minutes after an amidated calcium pectinate coat was applied; a comparable coat on large pellets showed a T50 of 93 minutes. Drug release profiles of dry coated pellets showed a lag time (all less than 20 minutes) when the gel coat hydrated and swelled, followed by a zero-order release. It was found that the release rate was controlled by the pellet size, pectin type, pectin concentration, and dissolution medium.

The impact of obesity on outcome after major colorectal surgery.

PURPOSE: There is an epidemic of obesity in the Western world and its associated substantial morbidity and mortality. This review examines the data on the impact of obesity on perioperative morbidity and mortality specifically in the context of colorectal surgery. METHODS: MEDLINE, PUBMED, and the Cochrane library were searched for relevant articles. A manual search for other pertinent papers also was performed. RESULTS: There is good evidence that obesity is a risk factor for wound infection after colorectal surgery. Obesity may increase the risk of wound dehiscence, incisional site herniation, and stoma complications. Obesity is linked to anastomotic leak, and obese patient undergoing rectal resections may be at particular risk. There is little data on the impact of obesity on pulmonary and cardiovascular complications after colorectal surgery. Operation times are longer for rectal procedures in obese patients, but hospital stay is not prolonged. Obese patients undergoing laparoscopic colorectal surgery are at increased risk of conversion to an open procedure. CONCLUSIONS: Obesity has a negative impact on outcome after colorectal surgery. To further clarify the impact of obesity on surgical outcome, it is recommended that future studies examine grades of obesity and include measures of abdominal obesity.

Effect of drug solubility on release behavior of calcium polysaccharide gel-coated pellets.

The aim of this study was to investigate the effect of drug solubility on the release behavior from calcium polysaccharide gel (CaPG)-coated pellets. Three different drugs with similar chemical structure, but different water solubility, namely caffeine (CAF), theophylline (TPL) and theobromine (TBR), were used. Drug-loaded spherical pellets were manufactured by an extrusion-spheronization method. The CaPG was applied on the pellets loaded with different drugs by interfacial complexation coating. The encapsulation efficiency of coated pellets was found to vary from 57.6 to 84.3%, depending on the solubility of the active drug and polysaccharide type. Drug release from different uncoated pellets was relatively unaffected by pH and release media but depended mainly on drug solubility. Release behavior was significantly modified in the pellets coated with CaPG, for all of the drugs tested. Drug release from coated pellets of the different drugs showed different release kinetics. The difference in the drug release is probably due to the difference in the drug dissolution within the core, before its partition and diffusion through the CaPG coat. The CAF dissolved faster and achieved a higher concentration in solution, which drove diffusion. The release of TBR from the coated pellets was much slower than that of the CAF or TPL because of its low solubility. However, the release of all drugs was about four- to sixfold slower for coated than uncoated pellets, suggesting that the coating influenced the retardation of drug release from the coated pellets. Therefore, the CaPG coating may provide a sustained release delivery system for all drugs tested.

Effect of selected non-ionic surfactants on the flow behavior of aqueous veegum suspensions.

The aim of this work was to investigate the influence of some non-ionic surfactants, Tween 80 and Brij 98, on the viscosity and flow behavior of a commercial montmorillonite clay, Veegum Granules. The effect of different concentrations of the surfactants on the shear stress-shear rate rheograms of hydrated concentrated clay suspensions was determined by shear viscometry. The addition of either surfactant increased the plastic viscosity and the yield stress of the suspensions. Furthermore, both surfactants altered the thixotropy of the suspensions to an extent that depended on both the surfactant concentration and the time of equilibration of the surfactant and Veegum. Brij 98 had a greater and more rapid effect. It is proposed that the surfactant polar head-groups anchor at the tetrahedral sheet surface, leaving the alkyl chains extending away from the edges and faces. Consequently, the alkyl chains undergo hydrophobic interactions that facilitate the association between the platelets and increase the physical structure within the suspension. Stereochemical differences between the polar groups may lead to differences in the way the surfactants associate with the tetrahedral sheet and hence their ultimate effect on the rheological behavior. There is a significant interaction between these surfactants and montmorillonite clays, and the rheological changes that occur could have a major impact on any pharmaceutical formulation that uses these ingredients.

Development of polysaccharide gel-coated pellets for oral administration. 2. Calcium alginate.

Calcium alginate gel-coated pellets were developed by forming an insoluble gel coat on extruded-spheronized pellets by interfacial complexation. Experiments were designed to investigate the effect of pellet size, alginate type, alginate concentration, and dissolution medium on swelling and drug release behavior. Low swelling in acidic media was related to proton-calcium ion exchange forming insoluble acid gels. In contrast, partial formation of soluble sodium alginate in 0.1M NaCl induced water uptake, resulting in greater swelling. Drug release from coated pellets showed a lag time when the gel coat hydrated and swelled, followed by a zero-order release. Significantly slower release was observed when either the pellet size or the alginate concentration was increased. Alginate with high guluronic acid content gave the slowest release. Different types of alginate with high mannuronic acid content showed different release behaviors that are probably due to the different monomer sequences and botanical sources. The faster drug release in acidic media and 0.1M NaCl compared to water is probably due to reduced calcium cross-linking in the gel. These results suggest that the pellet size, alginate type and concentration and dissolution medium influenced the swelling and drug release behavior of calcium alginate gel-coated pellets.

Development of polysaccharide gel coated pellets for oral administration 1. Physico-mechanical properties.

Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.

A novel gel formation method, microstructure and mechanical properties of calcium polysaccharide gel films.

Hydrophilic gels, formed by the interaction of calcium ions with either sodium alginate or potassium pectinate, can be deposited as a wet coating on to the surface of drug loaded pellets. If the coated pellets are dried, they could be dispensed to a patient in a capsule for oral delivery of the active drug. In contact with the aqueous fluids of the gastrointestinal tract, the gel coat will rehydrate, swell and will sustain the release of active drug from the core. In order to facilitate the development and refinement of this novel coated system, it is beneficial to have a method that can produce free gel films in a manner that closely mimics the way the gel coat is formed and deposited on the pellet surface. Traditional film producing methods would involve the spraying or depositing (by evaporation) the gel forming polysaccharide on to an inert surface, drying it and then exposing the dry film to a solution containing calcium ions. Because the film is dry before it is gelled, it is fundamentally different to the wet gel coats that are deposited on to the pellets. We have developed a method to produce wet gel films and have evaluated different manufacturing conditions in order to optimize the quality of the completed gel film. Additionally, we have used these films to assess the effect that the type of polysaccharide and the environmental conditions experienced during rehydration (pH and ionic strength) has on the mechanical properties and the microscopic morphology of the gel. Irrespective of the rehydration medium, the calcium pectinate gel films were softer, weaker and more porous, than the calcium alginate films. Although calcium alginate gels that were rehydrated in 0.1M NaCl were porous, the same films rehydrated in either water, simulated gastric fluid USP (without pepsin) or 0.1M HCl were stronger and much more dense microscopically. Furthermore, of the four different alginates that were evaluated, those with a high content of guluronic acid saccharides were the strongest but most brittle when rehydrated in water.

Computer-based real-time analysis in mobile ocular screening.

Mobile ocular telemedicine is potentially an effective method to provide service in medically underserved areas and to screen large populations for abnormalities. Currently, digital images are acquired, stored, and transferred to readers for evaluation, after which the results are provided to the subjects. The transfer of large image files and the timeliness of the subsequent reading of images are significant factors for practical implementation of effective telemedicine screening. This work examines the feasibility of in situ real-time computer analysis of digital images to determine and classify the image results as normal and abnormal. This retrospective study used a photoscreening database of 360 patients ranging in ages from 6 months to 18 years. Computer analysis automatically classified the binocular photorefraction (PR) images, and these PR results were compared to those of the subjective clinical eye examinations provided. With an average processing time of approximately 15 seconds per examinee, the analysis found that the PR results can be categorized as: a positive group that requires referral (186 cases) with a predictive value of 98.9% (2 false-positives); a negative group (144 cases) with a predictive value of 89.6% (15 false-negatives); and an uncertain group (30 cases or 8.3%) that required resolution by readers. The real-time analysis code reduces by approximately 92% the manpower for image grading and electronic transmission at this stage of ocular evaluation. These results indicate the feasibility of this approach.