Tissue Plasminogen Activator
The usage of TPA involves injecting it into the eye, particularly in the vitreous cavity or into the subretinal stratum. It helps to alleviate any damage received by the fibrin-mediated photoreceptors. One of the benefits of TPA is its relative safety, as the side effects are negligible when used at a dose below 50 mg (Rijken 300). However, should the dosage of TPA exceed 100 mg, it might be followed by retinal intoxication. The common symptoms of toxicity include the severe reduction in B-wave activity, exudative RD, and RPE hyperpigmentation. Some reports are different on that account. Goverdhan and Lochhead (210) report decreased levels of toxicity when using a dosage of 75 to 100 mg. Tsai et al. (723) mirror these observations in their research, where 100 mg dosage was applied to 15 patients with AMD. Two randomized control trials confirm a lack of toxicity in patients when dosage does not exceed 10 or 20 mg of TPA. The reason why TPA is such a safe product is that of its short period of half-life. The drug falls into its basic components in less than 5 minutes, which helps reduce chances of drug-drug interactions with medications that need to be injected into the subretinal space. However, it is recommended to avoid injecting TPA into the eyes within 72 hours after SMH due to the fact that it may cause internal bleeding. However, not doing so may cause additional damage to the eyes due to increased blood toxicity and fibrin meshwork contractions (Sternberg 720).
Intravitreal TPA and Gas
Intravitreal TPA and gas technique relies on the synergy of two symbiotic processes – the enzyme-induced lysis of the clot, which is caused by the effects of the TPA, and the use of a gas bubble in order to displace and remove liquefied blood out of the eye. According to the existing data, out of 256 patients who have undergone the combined therapy, every three out of four patients reported complete hemodisplacement. 21% of the patients were only partially affected by the therapy, whereas the remaining 6% reported no effect (Fujikawa et al. 1910; Regillo 184; Hassan et al.106; Hesse et al. 5; Hattenbach et al., 1490). There were significant VA improvements in 204, changing from 20/576 to 20/200. Optimal visual outcomes were obtained within 2 months. Negative outcomes were associated with various conditions that also had an effect on SMH, such as disc form scarring, atrophic AMD, and other underlying diseases. According to Hattenbach et al. (1490) and Tsai et al. (724), the most effective outcomes of treating SMH came within 14 to 21 days of treatment. The treatments usually failed when no significant progress was achieved in that time period. The combined therapy also has relatively few reported side effects and is considered to be less invasive when compared to other types of medical interventions against SMH. However, this method tends to have relatively short-term value, as it does not treat the underlying causes of the disease. Lastly, the mechanisms and methodology of implementation of the combined therapy are not fully studied, which diminishes its potential effect.
Vitrectomy and TPA and Blood Removal
Vitrectomy is the standard type of treatment used against SMH. It is a more intrusive and invasive procedure when compared to TPA and gas method. According to the available clinical data results, vitrectomy alone does not offer significant improvements when compared to the natural course of the disease (Peyman et al. 177). Typically, it is used in conjunction with TPA in order to dissolve the clot, which helps improve the effectiveness of the procedure. The usage of TPA helps make the procedure less invasive by reducing the need to create large retinotomy. The inherent risk of RD and PVR is also decreased. The technique was first reported by Peyman et al. (177), as one of the patients in their research saw an improvement from count fingers to 20/400. Other two patients have preserved their VA scores. Kamei et al. have modified the standard procedure by adding perfluorocarbon after the vitrectomy has been completed. This helped the percentage of successful outcomes significantly, with 81% of patients regaining vision, and only 1 patient losing it as a result.
Vitrectomy and Subretinal TPA and Gas
Studies regarding TPA and vitrectomy showed that TPA and gas had caused fewer cases of RD, but the percentage of vitreous haemorrhage was relatively high (9.8% out of 266 cases). Vitrectomy, on the other hand, has proven to have a higher percentage of RDs (5.7% versus 1.5%) but caused fewer cases of vitreous haemorrhages. This is because PPV helps relieve vitreomacular traction and increases oxygenations that reduce VEGF levels, which ensures complete or total SMH removal (Haupert et al. 210; Hillenkamp 7; Steel 637).
IntravitrealAnti-VEGF therapy
Antiangiogenic medications are often implemented in neovascular AMD therapies (Vander 139a; Vander 137b). Ranibizumab is a common agent that helps improve median VA after the treatment. In addition to that, anti-VEGF therapy may be solicited for patients with superior SMH due to late response times and for patients not suited to pneumatic displacement techniques or TPA therapy. Despite the fact that anti-VEGF injections are considered relatively safe, it is best to avoid them for patients with established structural foveal damage, as in that case, the risks of damage and discomfort do not justify the potential benefits of use.
Intravitreal anti-VEGF therapy and Gas
Several studies suggest the use of anti-VEGF therapy in combination with intravitreal therapy as a means of reducing risk and improving the efficiency of both. The expectations were that anti-VEGF therapy would help control the underlying disease while the pneumatic displacement would help remove the blood clot. As a result of the experiment, out of 29 patients and 3 to 12 month of therapy, around 76% showed partial hemodisplacement. Vision improved in 66% of the patients. The combined procedure is easy to implement and maintain and offers reasonable short-term results. However, the amount of patients participating in the research makes it hard to estimate the safety and efficiency of the proposed intervention (Chawla et al. 155; Hasler et al. 578; Mayer et al. 275; Nourinia et al. 168).
Intravitreal anti-VEGF Therapy, TPA, and Gas
Combining all three methods of therapy in order to treat VEGF and SMH has several promising advantages. All three methods do not require a specialized hospital setting and can be performed outside the hospital, or in a home setting. The drugs used in anti-VEGF, TPA, and gas therapies are cheap and readily available. Lastly, it is expected that these methods will prevent haemorrhages and improve patient outcomes. The available data suggest that the method is relatively safe and is extremely efficient, with 76% of hemodisplacement across 5 studies. Several researches find that the triple therapy produces the best results within the onset of 2 to 14 days (Nourinia et al. 168; Hampton and Delaney 235; Meyer et al. 491; Papavasileiou et al. 850; Sacu et al. 1407).
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