FcRn receptor-mediated pharmacokinetics of therapeutic IgG in the eye.

PURPOSE: The goal of this study was to determine the role of the neonatal Fc (FcRn) receptor in eliminating intravitreally administered full-length immunoglobulin G (IgG) across the blood-retinal barrier. METHODS: FcRn receptor expression in normal and laser photocoagulated retinas was compared quantitatively by real-time RT-PCR. The distribution of intravitreally administered full-length IgG was investigated and compared in wild-type and FcRn knockout mouse eyes as well as normal and laser-photocoagulated rat eyes at several time points. Additionally, the pharmacokinetics of intravitreally injected full-length IgG and chicken immunoglobulin Y (IgY) was compared in the normal rat retina. RESULTS: Intravitreally administered full-length IgG overcame the inner limiting membrane and diffused into the deeper retinal structures in both normal and laser-photocoagulated retinas. Interestingly, IgG was eliminated across the blood-retinal barrier into the blood system in the normal retina, whereas IgY was not. In addition, full-length IgGs did not penetrate across the blood-retinal barrier in the FcRn knockout mouse. Intravitreally injected IgGs were eliminated into the blood system more rapidly in laser-photocoagulated eyes when compared to normal control eyes because of FcRn receptor upregulation in the laser-photocoagulated retina. CONCLUSIONS: FcRn plays an important role in eliminating intravitreally administered full-length IgGs across the blood-retina barrier into the systemic blood system.

Mapping of the neonatal Fc receptor in the rodent eye.

PURPOSE: The neonatal Fc receptor (FcRn) has been known to modulate IgG transport and protect against IgG catabolism, resulting in extension of the serum half-life of IgG. The goal of this study was to localize FcRn receptor expression in the rat's eye. METHODS: The cornea, retina, conjunctiva, ciliary body and iris, retinal pigment epithelium and choroid, and lens were dissected from each rat's eye, and total RNA was purified. The first-strand cDNAs were synthesized and subjected to PCR reaction. For control samples, reverse transcriptase was omitted. A monoclonal antibody against the FcRn heavy chain was used to localize the distribution of the FcRn receptor in ocular tissues. Lymphatic vessels and blood vessels were stained with a rabbit anti-mouse lymphatic vessel endothelial receptor-1 polyclonal antibody and a rabbit anti-human von Willebrand factor polyclonal antibody, respectively. RESULTS: RT-PCR demonstrated expression of FcRn RNA in cornea, retina, conjunctiva, ciliary body and iris, and lens but absence of expression in the retinal pigment epithelium and choroid. Immunohistochemistry and double staining confirmed the expression of FcRn receptor to the conjunctival lymphatic vessels but not in the conjunctival blood vessels. In the ciliary body, the FcRn receptor was found to be expressed in both the nonpigmented ciliary epithelium and the ciliary blood vessels. The expression of FcRn receptor was confirmed in the retinal blood vessels, iris blood vessels, optic nerve vascular structures, corneal epithelium and endothelium, and lens epithelium. CONCLUSIONS: The FcRn receptor is expressed in multiple ocular tissues. The blood-ocular barrier showed FcRn receptor expression, indicating that IgG transport from ocular tissues to the blood system may use this receptor. The role of the FcRn receptor in the anterior segment and the conjunctiva remains unclear.

Vision-related impact on quality of life in an elderly patient population after corneal transplantation.

PURPOSE: The aim of this study was to assess the vision-related quality of life (QOL) and satisfaction of elderly patients who underwent corneal transplantations. METHODS: Survey data using a modified version of the Visual Function Index were collected in February-March 2013 from 175 patients (age ≥65 years) of 414 eligible patients who underwent corneal transplantation between 2008 and 2010 at the Wilmer Eye Institute. The survey assessed visual functionality, independence, and satisfaction. Transplant surgeries were limited to penetrating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), and keratoprosthesis. Sociodemographic and clinical data, including age, sex, initial and follow-up visual acuities, were collected. QOL survey measures were compared with patients' clinical findings to assess the differences between objective and subjective visual functioning. RESULTS: One hundred seventy-two patients were reviewed for surgery type. Eighty-six of 172 (50%) patients had follow-up data. Controlling for age, procedure, and baseline logarithm of the minimum angle of resolution (logMAR) visual acuity, patients treated by penetrating keratoplasty (P = 0.002) or keratoprosthesis (P = 0.019) were found to have poorer QOL scores than those treated with DSAEK. Age was positively associated with QOL improvement (P = 0.005). A relatively lower baseline vision (higher logMAR) was associated with a worse QOL (P < 0.001). When asked directly about their QOL, patients with relatively higher baseline vision (lower logMAR) reported no change in their QOL (P = 0.046). CONCLUSIONS: Type of surgery (DSAEK), older recipient age, and better baseline vision seem to be associated with an improved QOL in this study. Vision at follow-up is not associated with a QOL decline. Based on these findings, it is suggested that transplant surgery should be considered for elderly patients.

Surgical management of astigmatism with toric intraocular lenses.

Correction of corneal astigmatism is a key element of cataract surgery, since post-surgical residual astigmatism can compromise the patient's uncorrected visual acuity. Toric intraocular lenses (IOLs) compensate for corneal astigmatism at the time of surgery, correcting ocular astigmatism. They are a predictable treatment. However, accurate measurement of corneal astigmatism is mandatory for choosing the correct toric IOL power and for planning optimal alignment. When calculating the power of toric IOLs, it is important to consider anterior and posterior corneal astigmatism, along with the surgically induced astigmatism. Accurate toric lens alignment along the calculated meridian is also crucial to achieve effective astigmatism correction. There are several techniques to guide IOL alignment, including the traditional manual marking technique and automated systems based on anatomic and topographic landmarks. The aim of this review is to provide an overview on astigmatism management with toric IOLs, including relevant patient selection criteria, corneal astigmatism measurement, toric IOL power calculation, toric IOL alignment, clinical outcomes and complications.

Evaluation of clearance mechanisms with transscleral drug delivery.

PURPOSE: The goal of this study was to examine elimination pathways when delivering subconjunctivally administered hydrophilic agents to the retinas of rat eyes. METHODS: The distribution of sodium fluorescein released from an episcleral implant was compared in live and postmortem eyes. Elimination of the subconjunctivally administered hydrophilic agent IgG through blood and lymphatic vessels was investigated by immunohistochemistry. Additionally, lymphatic elimination of subconjunctivally injected sodium fluorescein was quantitatively evaluated. RESULTS: NaFl released from an episcleral implant was successfully delivered to the subretinal space in the postmortem eye but failed to do so in the live eye. Immunohistochemical visualization of the conjunctival tissue demonstrated dense distribution of blood and lymphatic vessels while also confirming the elimination of subconjunctivally administered IgG through these same vessels. The lymphatic elimination rate after injection of 75.6 µg of a hydrophilic agent, sodium fluorescein, into the subconjunctival space was determined to be 105 ng/min between 30 and 60 minutes. CONCLUSIONS: Conjunctival blood and lymphatic vessel elimination considerably limit transscleral hydrophilic drug delivery to the retina.

Investigating the movement of intravitreal human serum albumin nanoparticles in the vitreous and retina.

PURPOSE: To investigate the movement of intravitreally injected human serum albumin nanoparticles (HSA-NP) with respect to nanoparticle surface charge and retinal injury. METHODS: HSA-NPs were developed by a desolvation technique. HSA-NPs were cationized by covalent coupling of hexamethylenediamine on the particle surface. Either anionic or cationic HSA-NPs were injected to determine the effect of surface charge on intravitreal nanoparticle movement. HSA-NPs were injected intravitreally into both normal and laser photocoagulated eyes to examine the effect of the integrity of retinal tissue on the retinal penetration. The retinal penetration of fluorescence labeled anionic HSA-NPs was investigated by confocal microscopy. RESULTS: Anionic particles (-33.3+/-6.1 mV) more easily diffused through the 3-dimensional vitreal network of collagen fibrils than did their cationic counterparts (11.7+/-7.2 mV). In the laser photocoagulated retina, more HSA-NPs were detected in the choroidal space, compared to the normal retina. The immunohistochemical studies indicated that HSA-NPs were taken up into Müller cells. CONCLUSIONS: The movement of intravitreal nanoparticles depended on both nanoparticles surface charge and retinal injury. The Müller cells might play an important role in the retinal penetration of nanoparticles. The anionic HSA-NP is a promising drug or gene delivery carrier to the sub-retinal space and RPE.

Surgical management of astigmatism with toric intraocular lenses / Uso de lentes intraoculares tóricas no tratamento cirúrgico de astigmatismo

Correction of corneal astigmatism is a key element of cataract surgery, since post-surgical residual astigmatism can compromise the patient's uncorrected visual acuity. Toric intraocular lenses (IOLs) compensate for corneal astigmatism at the time of surgery, correcting ocular astigmatism. They are a predictable treatment. However, accurate measurement of corneal astigmatism is mandatory for choosing the correct toric IOL power and for planning optimal alignment. When calculating the power of toric IOLs, it is important to consider anterior and posterior corneal astigmatism, along with the surgically induced astigmatism. Accurate toric lens alignment along the calculated meridian is also crucial to achieve effective astigmatism correction. There are several techniques to guide IOL alignment, including the traditional manual marking technique and automated systems based on anatomic and topographic landmarks. The aim of this review is to provide an overview on astigmatism management with toric IOLs, including relevant patient selection criteria, corneal astigmatism measurement, toric IOL power calculation, toric IOL alignment, clinical outcomes and complications.

O tratamento do astigmatismo corneal é um fator importante na cirurgia de catarata, uma vez que o astigmatismo residual pode comprometer a acuidade visual não corrigida do paciente após a cirurgia. Lentes intraoculares (LIOs) tóricas compensam o astigmatismo corneal no momento da cirurgia, corrigindo o astigmatismo ocular. Ademais, constituem um tratamento previsível. Entretanto, é necessário obter uma medida precisa do astigmatismo corneal para selecionar o poder correto da LIO tórica e para planejar o melhor alinhamento da mesma. No cálculo do poder da LIO tórica, é importante considerar o astigmatismo das superfícies anterior e posterior da córnea, além do astigmatismo induzido na cirurgia. O alinhamento da lente tórica no meridiano planejado é essencial para se obter uma correção efetiva do astigmatismo. Há várias técnicas para guiar o alinhamento da LIO, incluindo a técnica de marcação manual tradicional e sistemas que se baseiam em pontos de referência anatômicos e topográficos. O objetivo desse artigo de revisão é discutir o uso de LIOs tóricas no tratamento de astigmatismo corneal, incluindo os critérios de seleção dos pacientes, a medida do astigmatismo corneal, o cálculo do poder da LIO tórica, o alinhamento da LIO tórica, os resultados clínicos e as complicações.