NPHP1-Related ciliopathies: A new case and major review of the ophthalmic manifestations of 147 reported cases.

Our case report and review contribute to the understanding of ocular manifestations in NPHP1 ciliopathies by reinforcing the relationship between pathogenic genetic variants and a wide array of ophthalmic abnormalities.

Ophthalmologic and facial abnormalities of Nicolaides-Baraitser syndrome.

BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS), first described in 1993, is a rare autosomal dominant disease caused by pathogenic variants in the SMARCA2 gene on chromosome 9p24.3. NCBRS typically presents with dysmorphic facial features, seizures, intellectual disability, and developmental delays. Abnormal findings of the eye and ocular adnexa associated with NCBRS have not been systematically evaluated and summarized in literature. This report presents the case of a 4-year-old male with NCBRS along with a systematic review of literature of the abnormal ophthalmologic and facial features of NCBRS cases. METHODS: A systematic review of literature of published cases of molecularly confirmed NCBRS was performed and the frequencies of eye, ocular adnexa, and facial abnormalities were calculated. RESULTS: Our patient's abnormal eye features include myopia, down slanting palpebral fissures, sagging inferior periorbital skin, hypertelorism, and long eyelashes. From the systemic review of literature, the most common abnormal eye and ocular adnexa features include prominent/long eyelashes, thick eyebrows, sagging periorbital skin, down slanting palpebral fissures, and ptosis. The most common facial dysmorphic features include thick/everted lower lip, coarse facial features, wide/large mouth, and thin upper lip. Dental abnormalities are also commonly reported. CONCLUSIONS: NCBRS frequently presents with well-defined ophthalmic and facial abnormalities. Prompt ophthalmologic evaluation following NCBRS diagnosis may be recommended to screen for several eye disorders. Surgical correction of ptosis may be indicated for NCBRS patients. This report may help further delineate the phenotype of this condition, which may allow for more rapid identification of those affected and provide incentive for additional studies.

Dry powder aerosol containing muco-inert particles for excipient enhanced growth pulmonary drug delivery.

Tenacious sputum poses a critical diffusion barrier for aerosol antibiotics used to treat cystic fibrosis (CF) lung infection. We conducted a proof-of-concept study using dense poly(ethylene glycol) coated polystyrene nanoparticles (PS-PEG NPs) as model muco-inert particles (MIPs) formulated as a powder using an excipient enhanced growth (EEG) strategy, aiming to minimize extrathoracic airway loss, maximize deposition in the airway and further overcome the sputum barrier in the CF lungs. The EEG aerosol formulation containing PS-PEG MIPs was prepared by spray drying and produced discrete spherical particles with geometric diameter of approximately 2 µm; and >80% of the powder dose was delivered from a new small-animal dry powder inhaler (DPI). The MIPs released from the EEG aerosol had human airway mucus and CF sputum diffusion properties comparable to the suspension formulation. These properties make this formulation a promising pulmonary drug delivery system for CF lung infections.

Therapeutic implications of nanomedicine for ocular drug delivery.

Delivering therapeutics to the eye is challenging on multiple levels: rapid clearance of eyedrops from the ocular surface requires frequent instillation, which is difficult for patients; transport of drugs across the blood-retinal barrier when drugs are administered systemically, and the cornea when drugs are administered topically, is difficult to achieve; limited drug penetration to the back of the eye owing to the cornea, conjunctiva, sclera and vitreous barriers. Nanomedicine offers many advantages over conventional ophthalmic medications for effective ocular drug delivery because nanomedicine can increase the therapeutic index by overcoming ocular barriers, improving drug-release profiles and reducing potential drug toxicity. In this review, we highlight the therapeutic implications of nanomedicine for ocular drug delivery.