An ocular insert with zero-order extended delivery: Release kinetics and mathematical models.

Ocular inserts (InEye®), were prepared based on two distinct formulations of PCL-PEG-PCL block copolymers - one with 33 % and the other with 24 % of PEG 600. Ring-open-polymerisation was used to link ε-caprolactone monomers to PEG hydroxyl end-groups. Molecular weight, PCL/PEG ratio, mass loss and swelling of different polymeric samples where determined. Based on the previously prepared block copolymers, ophthalmic inserts were assembled. These were prepared with an ellipsoidal shape by dripping melted polymer over a micro-tablet of moxifloxacin, used as drug model for this study, which therefore became entrapped in a central core coated with a polymer layer that functioned as a control-release barrier. The release kinetics of the model drug revealed a strong dependence on the PEG percentage on the polymer. Inserts' size and the amount of drug immobilized also had an important effect on the drug release profile. All release profiles followed a zero-order pattern, with 95 % of the drug being release at a constant rate. With drug releases varying from 20 to 200 days, and no initial burst, InEye® performance is unique among drug delivery systems and seems to be a very promising new formulation technology for preparing tailor-made ophthalmic inserts for prolonged and constant release of drug, which is needed for chronic diseases such as glaucoma, where compliance to treatment is essential for preventing optic-nerve lesions.

Ocular Manifestations and Therapeutic Options in Patients with Familial Amyloid Polyneuropathy: A Systematic Review.

PURPOSE: This paper aims to review the morphological and functional characteristics of patients affected by familial amyloid polyneuropathy (FAP), with greater focus on type I and its progression after liver transplantation. We also analyse therapeutic options for the ophthalmic manifestations. METHODS: The literature from 2002 through 2015 was reviewed, with a total of 45 articles studied, using the key terms related to amyloidosis and its therapeutic approaches. Information was collated, evaluated, critically assessed, and then summarised in its present form. PATHOPHYSIOLOGY AND TREATMENT: FAP results from mutation of the transthyretin gene, with Val30Met being the most frequent substitution. The symptoms are those typical of a sensorimotor autonomic neuropathy and can be halted with liver transplantation. Nowadays there are new medical therapies that delay the progression of the systemic neuropathy. However, there are still no options to avoid ocular disease. CONCLUSION: The main ocular manifestations in patients with FAP type I are amyloid deposition in the vitreous, dry eye, and secondary glaucoma. Despite liver transplantation, eye synthesis of amyloid persists and is associated with progressive ocular manifestations, which require continued ophthalmologic follow-up. New therapeutic strategies are therefore needed, particularly to target the ocular synthesis of the abnormal protein.

[Limbal transplantation: multicenter retrospective case series analysis]. / Estudio multicéntrico retrospectivo sobre trasplante de limbo.

PURPOSE: To report the results of limbal transplantation (LT) in patients with limbal stem cell deficiency (LSCD) in the context of ocular surface diseases. MATERIALS AND METHODS: A multicenter (5 centers) retrospective case series analysis of patients who underwent LT between 1996 and 2004 was performed. Data were collected by the same researcher using a customized database. Success was defined by the absence of a persistent corneal epithelial defect, on-going inflammation or recurrence of a pterygium. RESULTS: Data from 72 LT performed in 61 patients (65 eyes) with a mean follow-up of 20.8 months (SD 23.5; range, 3-115) were analyzed. There were 33 males and 28 females with a mean age of 55.8 years (SD: 15.6; range, 20-89). Fifty-eight (80.6%) LT were autografts (40 pterygia, 12 alkali burns, 3 iatrogenic cases, 2 viral infections, 1 neoplasia case) and 14 (19.4%) were allografts from cadaveric donors (7 immune-based disorders, 6 alkali burns, 1 iatrogenic case); all patients receiving allografts also received systemic immunosuppression. Of the total number of LT, 48 (66.7%) were successful. This proportion increased to 81.0% (47/58) when autografts were used. However, only 7.1% (1/14) of all allografts were successful. The success rate was higher (80.0%) when performed for a pterygium and lower when done for immune-based inflammation (14.3%). CONCLUSION: Autograft tissue for LT is always preferable to allografts to surgically treat LSCD, as clinical success is significantly higher, and systemic immunosuppression is avoided. As expected, immune-based disorders are the most difficult cases to treat. LT has been shown to be an excellent option for recurrent pterygium, although prospective studies need to be performed to further corroborate these results.

Estudio multicéntrico retrospectivo sobre trasplante de limbo / Limbal transplantation: multicenter retrospective case series analysis

Objetivo: Revisar el resultado de los trasplantes de limbo (TL) realizado en pacientes con Síndrome de insuficiencia límbica (SIL) en el contexto de varias enfermedades de la superficie ocular. Materiales y métodos: Se realizó un estudio retrospectivo y multicéntrico (cinco centros) de los TL realizados entre 1996 y 2004. Los datos fueron recogidos por el mismo investigador, en una base de datos especialmente diseñada para el estudio. Se consideró como «éxito» del TL a la ausencia de: defectos epiteliales, inflamación y recurrencia del pterigión cuando éste fue la causa del TL. Resultados: Se analizaron un total de 72 TL realizados en 61 pacientes (65 ojos) con tiempo de seguimiento de 20,8 meses (DS 23,5; rango, 3-115).Hubo 33 hombres y 28 mujeres, con una media de55,8 años (DS: 15,6; rango, 20-89). Se realizaron58 (80.6%) TL autólogos (40 pterigión, 12 causticaciones, tres iatrogénicas, dos infecciones virales, una neoplasia) y 14 (19,4%) TL alogénicos de donante cadáver (siete inflamaciones inmunes, seis causticaciones, uno iatrogénico). Todos los pacientes a los que se les realizó TL alogénicos recibieron inmunosupresión sistémica. Al final del seguimiento,48 (66,7%) TL se consideraron un éxito. Este porcentaje fue del 81,0% (47/58) en los TL autólogos y del 7,1% (1/14) en los TL alogénicos. El porcentaje de éxito también dependió de la etiología, siendo alto en los casos de pterigión (80,0%) y menor en las patologías inmunológicas (14,3%).Conclusiones: El TL autólogo es preferible al alogénico, pues la tasa de fracasos disminuye notablemente y, además, se evita el uso de inmunosupresión oral mantenida. Además, el pronóstico es siempre peor en los casos de patología inflamatoria inmune. El TL autólogo parece ser una buena elección para el tratamiento del pterigión recurrente, aunque se necesitan estudios prospectivos que corroboren estos resultados

Purpose: To report the results of limbal transplantation (LT) in patients with limbal stem cell deficiency (LSCD) in the context of ocular surface diseases. Materials and methods: A multicenter (5 centers) retrospective case series analysis of patients who underwent LT between 1996 and 2004 was performed. Data were collected by the same researcher using a customized database. Success was defined by the absence of a persistent corneal epithelial defect, on-going inflammation or recurrence of a pterygium. Results: Data from 72 LT performed in 61 patients(65 eyes) with a mean follow-up of 20.8 months(SD 23.5; range, 3-115) were analyzed. There were33 males and 28 females with a mean age of 55.8years (SD: 15.6; range, 20-89). Fifty-eight (80.6%)LT were autografts (40 pterygia, 12 alkali burns, 3iatrogenic cases, 2 viral infections, 1 neoplasiacase) and 14 (19.4%) were allografts from cadaveric donors (7 immune-based disorders, 6 alkali burns, 1 iatrogenic case); all patients receiving allografts also received systemic immunosuppression. Of the total number of LT, 48 (66.7%) were successful. This proportion increased to 81.0% (47/58)when autografts were used. However, only 7.1%(1/14) of all allografts were successful. The success rate was higher (80.0%) when performed for apterygium and lower when done for immune-based inflammation (14.3%).Conclusion: Autograft tissue for LT is always preferable to allografts to surgically treat LSCD, as clinical success is significantly higher, and systemic immunosuppression is avoided. As expected, immune-based disorders are the most difficult casesto treat. LT has been shown to be an excellent option for recurrent pterygium, although prospective studies need to be performed to further corroborate these results

Organic anion transport and reabsorptive fluid flux in diabetic retinal vessels: a microperfusion study.

Microperfusion techniques were used to characterize in vitro the fluorescein transport and fluid movement across isolated diabetic rabbit retinal vessels. Unbranched segments of arterioles of alloxan-induced diabetic rabbits were isolated and cannulated on a microperfusion apparatus. Movement of 3H-inulin, the reference tracer, and 14C-fluorescein, the test tracer, across the vascular walls was studied using microperfusion techniques adapted by us to study vascular permeability. The diabetic retinal vessels showed a fluid flux from bath to lumen of 3.6 +/- 0.6 nl min-1 mm-1 with perfusion rates of 7.1 +/- 0.3 nl min-1. This value was 43% (P < or = 0.05) lower when compared with normal values obtained in previous work. Bath to lumen fluorescein fluxes were 2.1 +/- 0.5 and 7.6 +/- 1.6 x 10(-12) mol min-1 mm-1, for fluorescein concentrations of 0.87 x 10(-4) and 1.5 x 10(-4) M, respectively. These values are 23% (P < or = 0.05) and 38.7% (P < or = 0.05), respectively, lower when compared to values obtained from normal retinal vessels. Probenecid, a competitive inhibitor of organic anion transport, added to the bath, had no effect. Increasing bath concentrations of fluorescein caused increasing fluid flux from bath to lumen, and again, probenecid added to the bath has no effect. These results show a significant decrease of fluorescein transport and of net fluid flux across diabetic retinal vessel walls from outside into the lumen, suggesting that in experimental alloxan-induced diabetes there is an early, probably functional, involvement of the retinal vessels in the initial alteration of the blood-retinal barrier (BRB).

Photorefractive keratectomy for myopia in 98 eyes.

Photorefractive keratectomy (PRK) was performed on 98 consecutive normal myopic eyes with the Summit OmniMed laser System. The minimum follow-up was 3 months and 31 were followed for 6 months. Preoperative myopia ranged from -1.25 to -12.00 D. The myopic eyes were divided into 4 groups according to the amount of myopia: group 1 (-1.25 to -3.00 D), 17 eyes; group 2 (-3.12 to -6.00 D), 42 eyes; group 3 (-6.12 to -9.00 D), 29 eyes and group 4 (> 9.00 D), 10 eyes. In group 1 mean uncorrected visual acuity was 0.87 at 3 months, 1.0 at 6 months and all of the eyes were within 0.50 D of the attempted correction. In group 2 mean uncorrected visual acuity was 0.76 at 3 months, 0.87 at 6 months and 92.3% of the eyes were within 0.50 D of the attempted correction. In group 3 mean uncorrected visual acuity was 0.65 and 0.66 at 3 and 6 months respectively and 77.8% of eyes were within 0.50 D of the attempted refractive correction. In group 4, mean uncorrected visual acuity was 0.46 and 0.7 at 3 and 6 months, respectively, and 100% were within 0.50 D of the attempted correction. Two eyes lost 2 lines and 4 eyes gained 2 or more lines of their preoperative best spectacle corrected visual acuity. Three eyes exhibited steroid induced rise in intraocular pressure that was controlled with topical timolol. No serious complications occurred. Despite the short follow-up, photorefractive keratectomy with the 193 nm excimer laser appears to be an effective and safe treatment for the correction of myopia.

Astigmatism after penetrating keratoplasty. Role of the suture technique.

The Authors retrospectively evaluated the evolution of corneal astigmatism 6, 12 and 24 months after penetrating keratoplasty in 75 eyes by comparing 2 suture techniques: running suture (RS) in 14 cases vs interrupted suture (IS) in 61 cases. The mean keratometric astigmatism in patients with RS was 7.75 +/- 3.10 D at 6 months, 5.89 +/- 2.50 D at 12 months and 3.90 +/- 1.70 D at 24 months. In patients with IS these values were 4.82 +/- 4.00 D at 6 months, 2.81 +/- 1.60 D at 12 months and 2.77 +/- 1.34 D at 24 months. A significant lower astigmatism (P < 0.05) was noted after using IS at 6 and 12 months. At 24 months, however, this difference was no longer statistically significant (P > 0.3). The IS suture allowed a better control of the post-surgical astigmatism, and a more rapid recovery of the visual acuity.

[Postmortem orbital hematomas]. / Hematomas orbitários post mortem.

Several cases of post mortem hematoma resulting from harvesting of the eye globes for transplantation, and susceptible of being misinterpreted as representing ante mortem trauma, are presented. Based on these cases the authors make a few considerations about the mechanisms of their production and technical procedures to avoid them.

Microperfusion studies on the permeability of retinal vessels. A new model demonstrating organic anion transport and a reabsorptive fluid flux.

We developed an experimental model to study the permeability of individual retinal vessels in vitro using microperfusion techniques adapted from kidney tubule studies. The retinal vessels were isolated by freehand dissection and mounted on a microperfusion apparatus. When inulin was perfused luminally, it was diluted to 80.2 +/- 2.3% of its initial concentration. However, no radioactive leak into the bath side was observed, suggesting that the dilution was due to fluid flux from bath to lumen. The dilution of fluorescein (81.9 +/- 3.8%) was in the same range as that of inulin, the reference marker. The extremely low lumen-to-bath fluorescein flux, 0.5 +/- 0.9 X 10(-12) mol/min/mm, increased by 68% when probenecid was added to the perfusate and by 210% when probenecid was placed in the bath. The effect was concentration-dependent. When placed in the bath, fluorescein moved rapidly across the retinal vessel walls, accumulating in the lumen to concentrations 40 times higher than in the bath. This movement from bath to lumen, which was much higher (13.6 +/- 0.3 X 10(-12) mol/min/mm) than the lumen-to-bath fluorescein flux for the same fluorescein concentration, decreased by adding probenecid to the bath. The kinetics of this unidirectional movement of fluorescein were consistent with a saturable active transport process. The fluid flux from bath to lumen across the retinal vessels, which was 6.3 +/- 1.0 nl/min/mm for perfusion rates of 6.6 +/- 0.2 nl/min, was temperature-dependent and was coupled to the fluorescein transport. Fluorescein stimulated the fluid flux by 17% when added to the perfusate and by 60% when added to the bath, and this effect could be reversed by probenecid. Our results showed an active transport of fluorescein in the rabbit retinal vessels coupled with net fluid flux from outside the vessels into the lumen.

Microperfusion studies of normal retinal vessels. D-glucose transport.

An experimental model was developed to study the permeability of individual retinal vessels in vitro using microperfusion techniques adapted from the kidney tubule studies. Inulin was used as the reference tracer and D-glucose as the test tracer. We found a concentration dependent flux of D-glucose from lumen to bath that increased as D-glucose concentrations in the lumen rose. The flattening of the hyperbolic curve at the higher D-glucose concentrations in the lumen appears consistent with the Michaelis-Menten equation (Km = 6 x 10(-3) M).

[Quantification of the foveolar zone in normal and diabetic patients]. / Quantification de la zone avasculaire centrale chez les sujets normaux et diabétiques.

The AA studied the foveolar avascular zone (FAZ) in diabetic patients using digital image processing (512 x 521) and comparing different methods of measurements. The results obtained from eighteen diabetic patients and twelve healthy nondiabetic controls were compared. Each patient was submitted to fluorescein angiography. The foveal avascular zone was quantified both, digitalized or by manual procedure. The different methods of analysis are compared and the results presented.