Use of PROSE for long-term ocular surface support in patients with a permanent keratoprosthesis.

Purpose: To describe the long-term outcome of the use of a specialized scleral lens known as a prosthetic replacement of the ocular surface ecosystem (PROSE) device to support the ocular surface in patients with a Boston Keratoprosthesis (KPro) Type I. All patients in this series were unable to pursue continuous wear of a bandage soft contact lens (BSCL) - a critical aspect of post KPro implantation management intended to protect the corneal carrier tissue from desiccation and stromal melting. Observations: Four eyes of four patients with a Boston KPro Type I were included. All four had failed BSCL wear and were instead treated with PROSE device wear. All four patients had underlying diagnoses associated with a diseased ocular surface (Stevens-Johnson Syndrome [one patient], prior failed penetrating keratoplasty associated with herpes zoster-related neurotrophic keratopathy [one patient], and prior failed penetrating keratoplasty associated with severe dry eye disease [two patients]). Causes of failure of BSCL wear included poor retention, discomfort, and poor vision. PROSE device wear was initiated on average seven and a half (range four to 14) months post-KPro implantation. The wear schedule varied and ranged from waking-hour wear only to 24-h wear. The average duration of device wear was 59.3 (range 28-103) months. Two patients exhibited persistent corneal epithelial defect formation with waking-hour wear, which resolved within 10 days with 24-h device wear. All patients exhibited improvement in vision with PROSE compared to baseline, averaging six and a half (range six to eight) lines of improvement in Snellen acuity, and all patients reported increased comfort. There was no incidence of microbial keratitis, KPro device instability, or other complication throughout the duration of device wear. Conclusions and Importance: This report offers a novel alternate approach to long-term support of the ocular surface in patients with a Boston KPro who fail standard continuous BSCL wear.

Treatment and Management of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome With Scleral Prosthetic Devices.

ABSTRACT: This case report highlights the unique application and long-term benefits of customized scleral devices in a patient with ocular complications from ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome over the span of 10 years. A 13-year-old girl with a history of EEC syndrome and ocular manifestations, including severe bilateral dry eye disease, corneal neovascularization and scarring, progressive fibrous pannus, and limbal stem cell deficiency, was examined and fitted with scleral devices. The goal of treatment was to stabilize the ocular surface, enhance vision, and improve ocular comfort. Throughout the course of treatment, there was minimal progression in ocular signs, despite interruptions in scleral device wear from application and removal challenges secondary to ectrodactyly. Customized scleral devices provided an optimal environment to support the ocular surface, improve comfort, and improve visual acuity. Further studies are required to demonstrate the benefits of scleral devices in larger populations of patients with EEC syndrome.

Tear Exchange, Intraocular Pressure, and Wear Characteristics of Quadrant-specific Versus Spherical Haptic Scleral Lenses.

OBJECTIVES: To compare scleral lenses (SLs) with a quadrant-specific (study lens) or a spherical (habitual lens) landing zone in a crossover study. METHODS: Seven participants (eight eyes) wore each of two lenses for 2 weeks before measurements. We measured visual acuity, contrast sensitivity, intraocular pressure (IOP), fluid reservoir clearance, corneal thickness, tear exchange, and lens experience. Variables were compared between lenses and before and after 2 hr of wear. RESULTS: The visual acuity was not different between the study lens, 0.12 logarithm of the minimum angle of resolution (logMAR), and habitual lens, 0.18 logMAR (median, P = 1.0). Contrast sensitivity was 1.3% under the study lens and 1.6% under the habitual lens ( P = 0.94). IOP did not change after 2 hr of wear for either lens (study lens, P = 0.33 and habitual lens, P = 0.74), and corneal thickness did not change during wear of either lens ( P = 0.44). The fluorescein concentration under the study lens did not change after 2 hr (99% of initial concentration; P = 0.84) but decreased to 46% of initial concentration under the habitual lens ( P = 0.008). Lens comfort was slightly better with the study lens (5.0 vs. 4.0, respectively; P = 0.05). CONCLUSIONS: SLs with spherical or quadrant-specific landing zones provide good vision and do not affect IOP or corneal thickness. However, tear exchange is greater under spherical lenses than under quadrant-specific lenses. The quadrant-specific lens provides greater patient comfort.

Regression of corneal opacity and neovascularization in Stevens-Johnson syndrome and Toxic Epidermal Necrolysis with the use of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment.

Purpose: To report two cases demonstrating the regression of corneal neovascularization and clearing of corneal opacification in patients with Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) undergoing prosthetic replacement of the ocular surface ecosystem (PROSE) treatment. Observations: Four eyes of 2 patients were analyzed. Regression of neovascularization and clearing of corneal opacification was observed in both patients. All 4 eyes demonstrated improvement in visual acuity with treatment. With treatment, both patients ultimately discontinued all prescribed topical therapies. It was discovered upon review of these cases that all 4 eyes were managed with PROSE devices designed with back-surface channeled haptics. Conclusions and Importance: There currently is no known literature reporting on long-term regression of corneal neovascularization or clearing of corneal opacity in SJS or TEN patients with the use of scleral prosthetic devices. This report of 2 cases highlights the improvement in corneal function with PROSE treatment involving the use of channeled designs in patients with SJS or TEN. More research is needed to better understand how PROSE or scleral lens design features affect patient outcomes and why some patients may show regression in corneal neovascularization.

A multi-parameter grading system for optimal fitting of scleral contact lenses.

Background: While scleral lens practise has improved over the years due to factors such as availability of lenses with better materials and designs as well as experience of practitioners, a lack of objectivity appears to remain in terms of assessment of scleral lens fitting. This prospective observational work aimed to achieve standardization on this front through proposing a grading system for scleral lens fitting. Methods: After application of prosthetic replacement of ocular surface ecosystem (PROSE) devices on the participants' eyes, four fundamental components for understanding scleral lens fitting such as central and limbal corneal clearance, mid-haptic compression, and alignment of lens edge over anterior sclera were assessed through a series of slit-lamp biomicroscopy imaging as well as with anterior segment optical coherence tomography. FitConnect® was used to modify the device parameters to simulate different grading patterns on the proposed scale. Serial imaging was done for all the different lenses to compose the grading scale. Results: A clinically relevant grading scale was constructed that pictorially demonstrated grades for the different aspect of scleral lens fitting. The grades were conveniently scaled within three categories: "optimal", "acceptable" and "not acceptable". Conclusion: The gradation of scleral lens fitting parameters would take a step towards objectifying the assessment patterns in practise. This will also help reducing the gap between a novice and an experienced practitioner in terms of understanding of scleral lens fitting.

OSDI Outcomes Based on Patient Demographic and Wear Patterns in Prosthetic Replacement of the Ocular Surface Ecosystem.

PURPOSE: To evaluate the impact of prosthetic replacement of the ocular surface ecosystem (BostonSight PROSE) treatment on symptom outcomes based on the Ocular Surface Disease Index (OSDI). PATIENTS AND METHODS: This was a single-center, retrospective analysis of consecutive patients who initiated PROSE treatment between September 2017 and December 2019 by the same clinician. The primary outcome measure was to compare OSDI survey scores at baseline prior to PROSE treatment and at follow-up, after PROSE treatment. Indication for treatment, sex, age, device diameter, average wear time, preexisting mental illness, duration of PROSE wear, and status of PROSE wear at follow-up were also studied. RESULTS: A total of 134 patients underwent PROSE treatment and completed a baseline OSDI survey during the study period. Forty-three patients completed a follow-up OSDI survey and were included in the study analysis. The most common treatment indications were keratoconjunctivitis sicca (n=27) and corneal ectasia (n=16). Baseline average OSDI score was 56.9±23.7 for the 43 subjects who completed a subsequent OSDI survey. The last documented average follow-up OSDI for those 43 subjects was 23.8±15.6, median (IQR) of 22.9 (10.4 to 32.3), and a statistically significant 54.7±27.6% average improvement from baseline (p<0.01). All patients, except for two, showed improvement in OSDI score. Statistically significant improvement occurred regardless of underlying diagnosis with no statistically significant difference based on age, sex, mental illness, or device diameter and no statistical correlation with average wear time, or duration of PROSE wear. CONCLUSION: PROSE treatment improves visual function and symptom relief as demonstrated by the OSDI survey. Sex, age, preexisting mental illness, device diameter, average wear time, and duration of wear had no statistically significant impact on OSDI outcomes.

CLEAR - Medical use of contact lenses.

The medical use of contact lenses is a solution for many complex ocular conditions, including high refractive error, irregular astigmatism, primary and secondary corneal ectasia, disfiguring disease, and ocular surface disease. The development of highly oxygen permeable soft and rigid materials has extended the suitability of contact lenses for such applications. There is consistent evidence that bandage soft contact lenses, particularly silicone hydrogel lenses, improve epithelial healing and reduce pain in persistent epithelial defects, after trauma or surgery, and in corneal dystrophies. Drug delivery applications of contact lens hold promise for improving topical therapy. Modern scleral lens practice has achieved great success for both visual rehabilitation and therapeutic applications, including those requiring retention of a tear reservoir or protection from an adverse environment. This report offers a practical and relevant summary of the current evidence for the medical use of contact lenses for all eye care professionals including optometrists, ophthalmologists, opticians, and orthoptists. Topics covered include indications for use in both acute and chronic conditions, lens selection, patient selection, wear and care regimens, and recommended aftercare schedules. Prevention, presentation, and management of complications of medical use are reviewed.

Case Report: Use of Prosthetic Replacement of the Ocular Surface Ecosystem Treatment of Traumatic Lid Ptosis in a Pediatric Patient.

SIGNIFICANCE: This report shares the long-term outcomes of an uncommon use of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment and scleral lenses in the treatment for patients with ptosis who are not surgical candidates. PURPOSE: This study aimed to describe a case of pediatric traumatic lid ptosis and follow-up during an 8-year period with PROSE treatment. CASE REPORT: A 7-year-old Honduran girl presented with a history of severe cranial, facial, and ocular trauma as a result of a motor vehicle accident. Significant ptosis with left-sided facial paralysis and irregular astigmatism significantly reduced the patient's visual function in the left eye. She was evaluated and treated with a scleral prosthetic device in the left eye to improve vision, the ocular surface, and overall function for activities of daily living. After 8 years of PROSE treatment, acuity in the left eye remained stable at 20/25. The corneal health remained stable throughout this period, without complications of corneal neovascularization or corneal edema. CONCLUSIONS: Prosthetic replacement of the ocular surface ecosystem treatment provided support of the ocular surface and mechanical left upper eyelid lift in a traumatic eyelid ptosis, ultimately providing improved visual function during an extensive 8-year period in a pediatric patient. Further studies are needed to evaluate the applicability of this approach in broader ptosis cases.

Clinical Outcomes of Scleral Lens Fitting with a Data-driven, Quadrant-specific Design: Multicenter Review.

SIGNIFICANCE: Alignment of the scleral lens haptic with the anterior ocular surface is of critical importance when fitting scleral lenses. The concept of leveraging big-data analysis to drive lens design is explored in this study. This retrospective study evaluated fitting outcomes of a data-driven, quadrant-specific scleral lens design and found that most patients (76%) were successfully fit with this design. PURPOSE: The purpose of this study was to evaluate clinical outcomes with a data-driven, quadrant-specific scleral lens design compared with traditional lens designs. METHODS: For this multicenter retrospective observational study, A REDCap (Research Electronic Data Capture) survey was distributed to scleral lens practitioners who participated in ß testing of a data-driven, quadrant-specific scleral lens design (study lens) between June 1, 2016, and January 31, 2017. Descriptive data were collected, and patient-reported outcomes, visual acuity, and lens design outcomes achieved with the study lens were described. RESULTS: Seventy-five patients (85 eyes) were fit with the study lens design between June 2016 and January 2017. Mean patient age was 47 years (range, 17 to 77 years). Forty-six were male, and 29 were female. Seventy-six eyes (89%) were fit for corneal irregularity, whereas nine eyes (11%) were fit for management of ocular surface disease. Compared with habitual correction, 22% more eyes achieved 20/20 or better, and 21% more eyes achieved 20/40 or better. There was also a 60% decrease in the need for midday removal with the study lens. An average of two lenses were manufactured per eye to complete the fitting process. CONCLUSIONS: Using a data-driven, quadrant-specific scleral lens resulted in visual improvement, a reduced need for midday removal, and an average of two lenses needed to complete the fitting process. Longer-term clinical outcomes and the use of big-data analysis to inform scleral lens design should be further explored.

Improvement of chronic corneal opacity in ocular surface disease with prosthetic replacement of the ocular surface ecosystem (PROSE) treatment.

PURPOSE: To demonstrate clearing of chronic corneal opacities and improvement of visual acuity with the use of BostonSight prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in ocular surface disease. OBSERVATIONS: We undertook retrospective analysis of the medical records of a series of patients who underwent PROSE treatment from August 2006 to December 2014. Patients were referred for ocular surface disease of various etiologies. Primary inclusion criterion was corneal opacity that improved with PROSE treatment. Patients were excluded if topical steroids or adjuvant therapy used once PROSE treatment was initiated. Underlying disease, prior treatment, clinical presentation, and clinical course were extracted from the medical record. Four patients are included in this series. There were three females and one male; median age at time of treatment initiation was 30 years (range = 0.5-58 years). Median duration of PROSE treatment at time of retrospective analysis was 3.5 years (range = 1-8 years). Two cases had corneal opacification in the context of neurotrophic keratopathy: a unilateral case due to presumed herpes simplex keratitis and a bilateral case due to congenital corneal anesthesia associated with familial dysautonomia. One case had corneal opacity from exposure related to seventh nerve palsy, and one had corneal opacification associated with recurrent surface breakdown, neurotrophic keratopathy, and limbal stem deficiency of uncertain etiology. After consistent wear of prosthetic devices used in PROSE treatment for support of the ocular surface, visual acuity improved and clearing of the opacities was observed, without use of topical steroids or adjuvant therapy. CONCLUSIONS AND IMPORTANCE: These cases demonstrate clearing of chronic corneal opacity with PROSE treatment for ocular surface disease. This clearing can occur with no adjuvant therapy, suggesting that restoration of ocular surface function and integrity allows for corneal remodeling.

PROSE Treatment for Ocular Chronic Graft-Versus-Host Disease as a Clinical Network Expands.

BACKGROUND: Keratoconjunctivitis sicca occurs in 40% to 90% of patients with ocular chronic graft-versus-host disease (cGVHD). Ocular symptoms can have profound effects in both the visual function and quality of life of patients with GVHD. We report the impact of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in patients with cGVHD as a clinical network expands. METHODS: We queried the BostonSight PROSE manufacturing database from January 2002 to December 2011. Patients treated for ocular cGVHD were reported by age, gender, year, and network site where the treatment was undertaken. The baseline and six-month follow-up scores of visual function using a standardized validated instrument, the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), were evaluated for a period in 2006 and again in 2010 after network expansion had occurred. RESULTS: A total of 407 patients with a male:female ratio of 226:181, mean age was 51 years with ocular cGVHD underwent PROSE treatment from January 2002 to December 2011. By 2011, 67% of all cases were treated at network clinics. Baseline characteristics of patients treated throughout the network in 2010 were similar to that of 2006 and 2010 cohorts from the main center. There was a significant improvement of 41 points (P<0.001) in composite NEI VFQ score among patients treated across the network in 2010, similar to the improvement of 30 points (P<0.001) seen among the patients treated at the main center in 2010. There was a trend toward lower baseline self-reported general health status (SRGHS) and VFQ scores among patients treated at network clinics, suggesting that expansion of the network allows treatment of sicker patients (lower general health status) or those more severely affected by ocular cGVHD. CONCLUSIONS: PROSE treatment of ocular cGVHD has increased in the last decade with the establishment of BostonSight network clinics across the United States. Patients treated at network clinics showed similar levels of baseline visual function and SRGHS, and achieved a similar high level of improvement in visual function as those treated at the main center. Patient-reported measures of functional status are useful in evaluating treatment options for patients with cGVHD. PROSE treatment has significant positive impact on the visual function of patients with ocular cGVHD regardless of whether the patient is treated at the main center or at a network site.

The effect of optic asphericity on visual rehabilitation of corneal ectasia with a prosthetic device.

OBJECTIVES: To study the effect of optic asphericity on visual rehabilitation of corneal ectasia with a prosthetic device. METHODS: Subjects with corneal ectasia treated with a fluid-ventilated gas-permeable prosthetic device of diameter 18.0-19.0 mm, who had subjective improvement of good Snellen vision with introduction of optic asphericity, were studied. Best corrected Snellen visual acuity (BCVA) under standard illumination, high contrast visual acuity (HCVA), low contrast visual acuity (LCVA), and wavefront aberrations were measured in a sequence of devices that varied per patient only in presence or amount of ellipsoidal front surface optical eccentricity (FSE). RESULTS: Five eyes of 5 subjects were studied. (M:F = 3:2; Age: 20-76). Mean steepest SimK was 57.72±8.30 D. BCVA was ≥20/30 in all eyes in all prosthetic devices, regardless of FSE. Although FSE improved BCVA, HCVA, and LCVA in each patient, no optimal amount could be identified in this small series. Asphericity in the form of 0.6 or 0.8 FSE improved HCVA, LCVA, or both in each patient. FSE was associated with a trend toward reduction of higher-order aberrations, particularly coma. CONCLUSIONS: Optic asphericity shows promise for optimization of vision in the rehabilitation of corneal ectasia with a prosthetic device.

Management of vascularized limbal keratitis with prosthetic replacement of the ocular surface system.

PURPOSE: To describe a case of contact lens-induced vascularized limbal keratitis (VLK) and management with prosthetic replacement of the ocular surface system (PROSE) treatment. METHODS: Clinical retrospective case report describing the clinical appearance, course of development, and treatment of VLK with PROSE. RESULTS: A 58-year-old white woman presented with a history of advanced keratoconus and almost four decades of contact lens wear, including polymethyl-methacrylate, small-diameter, gas-permeable lenses, low-Dk hybrid, and piggyback lens modalities. Complications of lens wear caused the development of extensive VLK in both eyes, with vascularization, lipid keratopathy, and corneal scarring projecting into the central cornea, more so in the left eye. She was evaluated and treated with PROSE in both eyes, demonstrating initial improvements in both comfort and vision, from 20/30 to 20/25 in the right eye and from 20/40 to 20/20 in the left eye. After 2 years of PROSE treatment, she reported excellent vision and comfort. Acuities were OD 20/25(+2) and OS 20/20(-/+). There was normalization of the corneal surface with reduced staining and epithelial irregularity, and there was substantial regression of corneal neovascularization and opacity, particularly in the left eye. CONCLUSIONS: PROSE, by normalizing the environment at the ocular surface, ultimately improved visual function and long-term ocular health for this patient.

The Boston Ocular Surface Prosthesis as a novel drug delivery system for bevacizumab.

Corneal neovascularization causes deterioration of visual acuity and increases surface irregularities. Various techniques have been employed to help control the progression of corneal neovascularization; bevacizumab is a medication that targets the specific pathway of corneal neovascularization. The Boston Ocular Surface Prosthesis (BOSP) is a large diameter contact lens that aids in maintaining corneal surface integrity and may serve as a delivery system for topical bevacizumab. This paper reviews five patients who were treated with topical bevacizumab in their BOSP. All patients demonstrated improvement in their visual acuity and clinical exam. No adverse reactions were noted.

Intacs for keratoconus and post-LASIK ectasia: mechanical versus femtosecond laser-assisted channel creation.

PURPOSE: To evaluate the efficacy of intracorneal ring segments to treat keratoconus and post-laser in situ keratomileusis (LASIK) keratectasia implanted by using either mechanical dissection or a femtosecond laser. METHODS: Thirty-three eyes of 29 patients had intracorneal ring segments implanted by using mechanical dissection (17 eyes) or a femtosecond laser (16 eyes). Mean follow-up was 10.3 months. Parameters assessed before and after surgery included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refractive spherical equivalent (MRSE), refractive cylinder (RC), best contact lens-corrected visual acuity (BCLVA), and contact lens tolerance. RESULTS: Statistically significant changes occurred for all parameters when we analyzed all 33 eyes as 1 group. Mean UCVA LogMar values improved from 1.0 +/- 0.3 (20/200) to 0.6 +/- 0.4 (20/80) (P < 0.0005). Mean BSCVA changed from 0.3 +/- 0.2 (20/40) to 0.2 +/- 0.2 (20/30) (10%; P < 0.05), and MRSE from -9 +/- 4 to -7 +/- 4 D (P < 0.05; 20%). There was a decrease of 0.5 D or more of RC in 62% of eyes. BCLVA improved from 0.2 +/- 0.2 (20/30) to 0.1 +/- 0.1 (20/25) after surgery (P < 0.02). Contact lens tolerance improved in 81% of eyes. There was no statistically significant difference in outcomes between mechanical dissection and femtosecond laser-assisted techniques. However, although statistical power was adequate to detect changes in clinical parameters as a result of surgery, it was not sufficient to conclusively show such differences between surgical techniques. CONCLUSIONS: For mild to moderate cases of keratoconus and post-LASIK keratectasia, the use of a femtosecond laser for Intacs channel creation seems as effective as mechanical dissection. Future studies are warranted to further evaluate channel creation by a femtosecond laser.

VEGF164 is proinflammatory in the diabetic retina.

PURPOSE: The objectives of this study were to characterize the differential potency of two major VEGF isoforms, VEGF(120) and VEGF(164), for inducing leukocyte stasis (leukostasis) within the retinal vasculature and blood-retinal barrier (BRB) breakdown and to determine whether endogenous VEGF(164) mediates retinal leukostasis and BRB breakdown in early and established diabetes. METHODS: Retinal leukostasis and BRB breakdown were simultaneously quantified by combining concanavalin A lectin (ConA) perfusion labeling with a fluorophotometric dextran leakage assay. CD45 immunohistochemistry was performed to confirm that ConA-stained cells within the vasculature were leukocytes. Retinal leukostasis and BRB breakdown were compared in nondiabetic rats receiving intravitreous injections of VEGF(120) or VEGF(164). Retinal intercellular adhesion molecule (ICAM)-1 and VEGF protein levels were studied by Western blot and ELISA, respectively. An anti-VEGF(164(165)) aptamer (EYE001) was administered by intravitreous injection to 2-week and 3-month diabetic rats, and the effect on retinal leukostasis and BRB breakdown was quantified. RESULTS: Compared with VEGF(120), VEGF(164) more potently increased retinal ICAM-1 levels (2.2-fold), leukostasis (1.9-fold), and BRB breakdown (2.1-fold, P < 0.01 for all), despite negligible differences in vitreoretinal VEGF levels at the time of evaluation (P > 0.05). Retinal leukostasis and leakage increased with the duration of diabetes (P < 0.01) and correlated closely (P < 0.01, r = 0.889). The isoform-specific blockade of endogenous VEGF(164) with EYE001 resulted in a significant suppression of retinal leukostasis and BRB breakdown in both early (72.4% and 82.6%, respectively) and established (48.5% and 55.0%, respectively) diabetes (P < 0.01). CONCLUSIONS: On an equimolar basis, VEGF(164) is at least twice as potent as VEGF(120) at inducing ICAM-1-mediated retinal leukostasis and BRB breakdown in vivo. The inhibition of diabetic retinal leukostasis and BRB breakdown with EYE001 in early and established diabetes indicates that VEGF(164) is an important isoform in the pathogenesis of early diabetic retinopathy.

Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic)acid microspheres.

PURPOSE: To develop a controlled-drug delivery system for the long-term inhibition of vascular endothelial growth factor (VEGF) and its mediated responses. METHODS: Poly(lactic-co-glycolic)acid (PLGA) microspheres containing anti-VEGF RNA aptamer (EYE001) formulations in the solid-state were developed by an oil-in-oil solvent evaporation process. In vitro experiments were performed to characterize the release profiles. Stability and bioactivity of the released drug were assayed by monitoring the RNA aptamer's ability to inhibit VEGF-induced cell proliferation in human umbilical vein endothelial cells (HUVECs). Cell proliferation experiments were conducted with aptamer aliquots collected after short-, mid-, and long-term release time points. To investigate the feasibility of this polymer device as a potential transscleral delivery device, an in vitro apparatus was developed to assess polymer hydration and degradation through rabbit sclera and subsequent delivery through it. RESULTS: PLGA microspheres were able to deliver EYE001 in a sustained manner, with an average rate of 2 micro g/d over a period of 20 days. Solid-state stabilization of the aptamer with disaccharide trehalose before lyophilization and encapsulation in PLGA rendered the drug more stable after release. Cell proliferation experiments demonstrated that the bioactivity of the aptamer was preserved after release, as indicated by inhibition of endothelial cell proliferation after incubation with VEGF. Microspheres packed into a sealed chamber and placed onto the "orbital" part of a rabbit sclera for a period of 6 days became hydrated and started to degrade, as shown by scanning electron microscopy (SEM). As a result, the aptamer was delivered from the microspheres through the sclera, as determined spectrophotometrically. CONCLUSIONS: The loading of aptamer-containing microspheres into a device and placing it on the orbital surface of the sclera was assessed and shown to be feasible. RNA aptamer EYE001 encapsulated in PLGA was delivered over a period of 20 days with retained activity. This method represents a promising approach for the transscleral delivery of drugs and the treatment of choroidal and retinal diseases.

Protein spray freeze drying. 2. Effect of formulation variables on particle size and stability.

Spray freeze drying produces protein particles suitable for microencapsulation into polymeric microspheres intended for sustained release. Accessibility of encapsulated protein particles to the microsphere surface increases as the protein particle size is increased. Thus, it is desirable that the encapsulated protein particle size be minimized to limit initial release. We have investigated the effect of formulation on spray freeze-dried bovine serum albumin (BSA) as a model protein. Atomization conditions were fixed such that in the absence of excipient, the particle size of the sonicated powder was submicron, and there was substantial protein degradation (loss of monomer). Addition of low concentrations of surfactants (up to the CMC) or mannitol (up to the point where it tended to crystallize upon dehydration) resulted in partial stabilization without impacting particle size. Trehalose was successful in stabilizing the protein; however, there was a marked increase in particle size at the highest levels tested. Ammonium sulfate provided partial stabilization, but also tended to form crystals and increase particle size. FTIR measurements showed a loss of native secondary structure upon spray freeze drying that was ameliorated by addition of trehalose. Other excipients did not prevent structural perturbations. In general, stabilization of spray freeze-dried BSA was related to lowering of the specific surface area in the powder. A balance must be achieved when spray freeze drying proteins intended for encapsulation in sustained-release systems.