In situ forming hydrogels are suitable candidates for increasing drug residence time in ocular drug delivery. In this study, gellan gum (GG) was oxidized to form aldehyde groups and in situ gelling hydrogels were synthesized based on a Schiff-base reaction between oxidized GG (OGG) and chitosan (CS) in the presence of β-glycerophosphate. The effect of OGG and CS concentration on the physical and chemical properties of the resulting hydrogels was investigated. The FT-IR spectroscopy confirmed the chemical modification of OGG as well as the functional groups of the prepared hydrogels. The scanning electron microscope (SEM) revealed the highly porous structure of hydrogels. The obtained hydrogels indicated a high swelling degree and degradability. Also, the rheological studies demonstrated self-healing behavior, shear thinning, thixotropy, and mucoadhesion properties for the developed hydrogels. The results of in vitro and ex vivo studies showed that the timolol-loaded hydrogel with a higher amount of OGG has a higher release rate. Moreover, the MTT cytotoxicity test on bone marrow mesenchymal stem cells (BMSCs) confirmed that developed hydrogels are not toxic. The obtained results revealed that the developed hydrogels can be a desirable choice for the ocular drug delivery of timolol in the treatment of glaucoma.

For the foreseeable future, timolol 0.5% nasal spray prepared by compounding pharmacists will be the only source for a potentially dramatic new paradigm in the treatment of acute migraine.1 It is also likely other medical conditions can be treated with the compounded timolol nasal spray that need extremely rapid therapeutic beta blocker blood levels when IV infusion is not possible or practical. This manuscript will review the research and development of compounded timolol medication over the past dozen years and reference previous articles in IJPC detailing how the pharmaceutical compounded product is prepared.2 A final goal is to engage physicians in a beneficial working relationship with compounding pharmacies to make immediately available to patients a nasal spray formulation of the beta blocker timolol 0.5% in solution. It has recently been demonstrated for the first time to benefit acute migraine treatment.

BACKGROUND: Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents.
OBJECTIVE: To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used.
METHODS: The Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016-2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had two photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores - both before and after treatment - as well as the outcomes percent considered excellent (>9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents\' assessments.
RESULTS: The median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p<0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p>0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever.
CONCLUSIONS: This is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the three therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.

Infantile hemangioma is a benign vascular tumor, the most common in childhood, whose natural evolution is the disappearance of the lesion in the pediatric age and which has effective and safe treatments that limit its growth and favor its disappearance at younger ages. Infantile hemangioma continues to be a reason for attention to complications, due to erroneous diagnoses, lack of knowledge of the condition, late referral or fear of the effects of the medications used for its treatment. Furthermore, its presence is normalized without taking into account that it can cause uncertainty, anxiety, feelings of guilt and, as a consequence, a significant impact on the quality of life, mainly in the parents or caregivers of the child. The need for a clinical practice guideline in our country arises from the high presentation of late-remitted complications in infantile hemangioma even with the availability of adequate treatments, the continuous evolution of medicine and the appearance of new evidence. Throughout the guide you will find recommendations regarding the diagnosis, treatment and follow-up of patients with infantile hemangioma, taking into account the paraclinical tests that can be performed, topical or systemic management options, as well as adjuvant therapies. For the first time, objective tools for patient follow-up are included in a guide for the management of infantile hemangioma, as well as to help the first contact doctor in timely referral.
El hemangioma infantil es un tumor vascular benigno, el más frecuente de la infancia, cuya evolución natural favorece la desaparición de la lesión en la misma edad pediátrica y que cuenta con tratamientos eficaces y seguros que limitan su crecimiento y favorecen su desaparición a edades más tempranas. Continúa siendo motivo de atención de complicaciones, debido a diagnósticos erróneos, desconocimiento del padecimiento, referencia tardía o temor de los efectos de los fármacos utilizados para su tratamiento. Además, se normaliza su presencia sin tomar en cuenta que puede llegar a causar incertidumbre, ansiedad, sentimientos de culpa y, como consecuencia, importante afectación de la calidad de vida, principalmente en los padres o cuidadores del niño. La necesidad de una guía de práctica clínica en nuestro país surge ante la alta presentación de complicaciones del hemangioma infantil referidas de manera tardía aun con la disponibilidad de tratamientos adecuados, la evolución continua de la medicina y la aparición de nueva evidencia. A lo largo de la guía se encontrarán recomendaciones en relación con el diagnóstico, el tratamiento y el seguimiento de los pacientes con hemangioma infantil, tomando en cuenta los paraclínicos que pueden realizarse, las opciones de manejo tópico o sistémico, y las terapias adyuvantes. Por primera vez se incluyen en una guía para el manejo del hemangioma infantil herramientas objetivas para el seguimiento de los pacientes, así como para ayudar al médico de primer contacto en su referencia oportuna.

OBJECTIVE: The objective of the study was to examine the effect of dorzolamide-timolol (DT) eye drop used before intravitreal ranibizumab (IVR) injection on intraocular pressure (IOP) change.
METHODS: 50 eyes of 50 patients who received DT eye drops 1 h before IVR injection due to diabetic retinopathy and macular edema were considered Group 1, and 50 eyes of 50 patients who did not receive DT eye drops were considered Group 2. Those patients who had previously undergone intravitreal injection had intraocular surgery, and used any eye drops were not included in the study. Before the injection, IOP values were measured with a Tonopen contact handheld tonometer before the blepharostat was placed (BIOP), after the blepharostat was placed (AIOP), and at the 1st min after the injection (IIOP).
RESULTS: There were 25 males and 25 females in Group 1 and 25 males and 25 females in Group 2; the mean age was 65.66 ± 9.94 years in Group 1 and 65.54 ± 7.43 years in Group 2 (P = 0.98). In Group 1, BIOP was 18.91 ± 18.91, AIOP was 21.62 ± 6.16 mmHg, and IIOP was 49.21 ± 10.95 mmHg. In Group 2, BIOP was 20.18 ± 4.19 mmHg, AIOP was 24.60 ± 4.90 mmHg, and IIOP was 49.96 ± 9.72 mmHg. IIOP-BIOP difference was 30.30 ± 9.85 mmHg in Group 1 and 29.78 ± 9.33 mmHg in Group 2 and the difference was not statistically significant (P = 0.78). In Group 1, the IIOP-AIOP difference was 27.58 ± 10.60 mmHg and in Group 2, 25.36 ± 10.46 mmHg. The difference between IIOP and AIOP was not statistically significant (P = 0.27).
CONCLUSIONS: The use of topical DT eye drops before IVR injection does not affect the intraocular pressure change.

Beta-blockers have been established as a treatment of infantile haemangiomas (IH) since its serendipitous discovery for use in IH in 2008. However, data on the safety of these beta-blockers for use in IH in preterm infants are scarce. A retrospective study was performed to review the safety of oral propranolol and topical timolol in the treatment of IH in a cohort of preterm infants treated at our tertiary paediatric hospital. It was observed that there was an increased risk of adverse events amongst the preterm infants with chronic lung disease, retinopathy of prematurity and gastroesophageal reflux, when treated with oral propranolol.

暂无摘要。

Pityriasis rubra pilaris (PRP) is a rare dermatological condition which may present with ocular manifestations. We report a case of recurrent cicatricial ectropion (CE) with topical beta-blocker use in the rare dermatological condition PRP. The patient underwent release of scar tissue, lateral tarsal strip and full-thickness supraclavicular skin graft for CE following immunosuppression with methotrexate for 3 months. Postoperatively, CE recurred, with skin graft shrinkage and resumption of periocular disease activity, 8 weeks following the introduction of topical timolol. The patient was referred for further immunosuppression and substitution of timolol before consideration for further surgery. PRP has a variety of potential ocular complications. Surgery has a high risk of recurrence and should be performed when the overall disease is quiescent and drugs, which could trigger reactivation, have been discontinued and/or substituted. Skin grafts should be oversized to off-set shrinkage.

暂无摘要。

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice.
OBJECTIVE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD.
METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection.
RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001).
CONCLUSIONS: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.
Протокол ведения пациентов с неоваскулярной формой возрастной макулярной дегенерации (нВМД) подразумевает многократные интравитреальные инъекции (ИВИ) анти-VEGF-препарата, возможность уменьшить пик повышения уровня внутриглазного давления (ВГД), имеет высокую значимость в клинической практике.
UNASSIGNED: Оценить влияние местного применения гипотензивных препаратов на кратковременное повышение уровня ВГД после ИВИ анти-VEGF-препарата у пациентов с нВМД.
UNASSIGNED: В проспективное исследование были включены 80 пациентов с впервые выявленной нВМД. Перед началом лечения пациенты были разделены на 4 группы по 20 человек в каждой: 1-я — контрольная, препараты с профилактической целью не применялись, во 2, 3 и 4-й группах местно проводились инстилляции одной капли в конъюнктивальную полость гипотензивных препаратов бринзоламида 1%, бринзоламид–тимолола, бримонидин–тимолола дважды: за 1 день до инъекции (в 20 ч) и в день инъекции за 2 ч до манипуляции (в 8 ч) соответственно. У каждого пациента измеряли уровень ВГД с помощью точечного контактного тонометра ICare Pro до инъекции, через 1, 30 и 60 мин после инъекции.
UNASSIGNED: Применение гипотензивных препаратов с профилактической целью ассоциировалось со значимым снижением уровня ВГД сразу после ИВИ по сравнению с аналогичным показателем в 1-й группе (p<0,001), максимальное снижение значений ВГД наблюдалось при использовании фиксированной комбинации бримонидин–тимолол на 12,1 мм рт.ст. по сравнению с данными контрольной группы (p<0,001), комбинация бринзоламид–тимолол снижала уровень ВГД на 8,5 мм рт.ст. (p<0,001), бринзоламид 1% приводил к наименьшему снижению показателей ВГД — на 5,1 мм рт.ст. (p<0,001).
UNASSIGNED: При применении инстилляций одной капли в конъюнктивальную полость за 1 день до инъекции и в день инъекции в группе, где применялась комбинация бримонидин–тимолол, наблюдалось максимальное снижение уровня ВГД в сравнении с данными других групп.