Treating Conditions of the Eye Case Study
When teaching a patient how to instill ophthalmic drops, it is important to carefully explain all the steps of this procedure. First of all, patients should thoroughly wash their hands with soap. Second, they should check the dropper tip and make sure that it is not cracked. Third, while tilting their head back, they should pull down the lower lid of the eye with the index finger in order to form a pocket. Fourth, they should hold the dropper with the other hand close to the eye but not touching it. Fifth, while looking up, they should squeeze the dropper gently so that one drop falls into the pocket. Sixth, they should close the eye for three minutes and keep their head down. Treating Conditions of the Eye Case Study.
In doing so, patients should not blink or squeeze the eyelids. Then, patients should wipe the excess liquid from around the eye and do the same operation with the other eye. Washing hands after the operation are also necessary (“How to use eye drops,” 2017).
The operation of instilling an ointment in the eye is similar. After lowering the lower eyelid, patients should hold the tube with an ointment upside down near to the eye and press the tube to release a line of ointment into the pocket. Then, patients should blink several times to spread the ointment. Treating Conditions of the Eye Case Study.The vision will become blurred, but soon it will become clear again. In doing this operation, patients should not rub their eyes (“How to use eye drops,” 2017).
In the case of small children and infants, it is also important to explain to parents that the vision will change and the stinging sensation will appear. Also, it is important to minimize distractions, as children can make a sudden move which will spoil the operation (“How to give eye drops,” 2017).
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Regarding the geriatric patients, it is important to take into account their health condition, as they may have poor vision, shaking hands, and even problems with the opening. In such cases, it is recommended that younger relatives do this operation for them (“How to give eye drops,” 2017).
CATARACTS
A cataract is a clouding of the lens in the eye that affects vision. Most cataracts are related to aging. Cataracts are very common in older people. By age 80, more than half of all Americans either have a cataract or have had cataract surgery. A cataract can occur in either or both eyes. It cannot spread from one eye to the other. Although most cataracts are related to aging, there are other types of cataract: 1. Secondary cataract- Cataracts can form after surgery for other eye problems, such as glaucoma. Cataracts also can develop in people who have other health problems, such as diabetes. Cataracts are sometimes linked to steroid use. 2. Traumatic cataract- Cataracts can develop after an eye injury, sometimes years later. 3. Congenital cataract- Some babies are born with cataracts or develop them in childhood, often in both eyes.Treating Conditions of the Eye Case Study. These cataracts may be so small that they do not affect vision. If they do, the lenses may need to be removed. 4. Radiation cataract- Cataracts can develop after exposure to some types of radiation. GLAUCOMA
Glaucoma is a group of diseases that damage the eye’s optic nerve and can result in vision loss and blindness. However, with early detection and treatment, you can often protect your eyes against serious vision loss. At first, open-angle glaucoma has no symptoms. It causes no pain. Vision stays normal. Glaucoma can develop in one or both eyes. Without treatment, people with glaucoma will slowly lose their peripheral (side) vision. As glaucoma remains untreated, people may miss objects to the side and out of the corner of their eye. They seem to be looking through a tunnel. Over time, straight-ahead (central) vision may decrease until no vision remains.
ASTIGMATISM
Astigmatism is a common type of refractive error. It is a condition in which the eye does not focus light evenly onto the retina, the light-sensitive tissue at the back of the eye. Astigmatism occurs when light is bent differently depending…
1.1 Glaucoma
Eye disease such as glaucoma, cataracts, age-related macular degeneration and diabetic retinopathy are some of the common causes of reduced vision and blindness (Short, 2008). Glaucoma is a progressive eye disease where the damage of optic nerves resulted in visual field loss. In the year of 2010, it is estimated that 60.5 million people will be diagnosed with glaucoma, and by 2020, the number would be increased to 79.6 million (Quigley and Broman, 2005). According to International Glaucoma Association, some of the risk factors that contribute to the development of glaucoma are advanced age, race, long or short sighted, and genetic predisposition. Damage of the optic nerves in glaucoma is often due to elevated intraocular pressure (IOP) which occurs when there is an imbalance of aqueous humor production and drainage in the eye. This clear fluid produced by the ciliary body flows into the posterior chamber and exit through trabecular meshwork at the open angle where the cornea and iris meet (1).Treating Conditions of the Eye Case Study. Blocked drainage channel restricts the flow of aqueous humor out of the anterior chamber. This causes the pressure in eye to be increased to an abnormal level, thus damaging the optic nerves. Optic nerve plays an important role in transmitting impulses from the light sensitive tissue layer, the retina to the brain, where the visual information is interpreted. Therefore, early detection and treatment could prevent permanent and irreversible blindness from glaucoma.
There are several classifications of glaucoma, the most common types are primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). The difference between these two types is the present of physical obstruction in the drainage channel in one and its absence in the other. As for the former type, an increase in IOP is caused by blockage of the drainage channel where the aqueous humor drains out (1) (Coleman,1999). This process occurs very gradually and often patient does not notice any early signs of sight loss such as blind spots, or patches of vision loss until severe damaged has been done to the optic nerves, thus causing blindness. Different ethnic group was shown to have different glaucoma prevalence. The African population was shown to be more prevalent to suffer from POAG in the study demonstrated by Ntim-Amponsah et al. (2004). The standardised age-specific glaucoma prevalence for that ethic group was 7.7% while the Caucasians have an overall lower prevalence than that. It was suggested by Herndon et al. (2004) that the blacks have an overall thinner central corneal compared to the Caucasians and this might contribute to the progression of POAG.
As explained by Coleman (1999), in primary angle-closure glaucoma (PACG), the angle between the iris and lens is very narrow. When the iris dilates, the iris-lens contact prevents the flow of aqueous humor into the anterior chamber. The continuous secretion of aqueous humor creates a pressure which pushes the iris forward onto the trabecular meshwork, closing the angle (1). This rapid onset causes sudden build-up of intraocular pressure leading to short-term loss of vision. Severe eye pain, blurred vision, headache, nausea, vomiting and halos around lights are among the symptoms observed in this eye disease. Treating Conditions of the Eye Case Study. Asian was shown to have a higher prevalence of PACG compared to the Western population. Some of the studies concluded that Chinese are at a higher risk of suffering from PACG. This is related to the geometry of the anterior chamber where Chinese has a smaller corneal or a shallower anterior chamber, thus implying that there is a higher risk of developing angle closure and therefore PACG (Wang et al., 2002).
1.2 Pharmacological therapy of glaucoma
The goal in treating glaucoma is to delay the progression by giving immediate therapy for early stage glaucoma patient to prevent further loss of vision. Treatment aims to reduce IOP by either increasing the aqueous humor drainage or reducing the aqueous humor secretion rate. Several classes of drugs are used in the treatment of glaucoma, namely beta-adrenergic antagonists (beta-blockers), selective alpha2-adrenoceptor antagonist, carbonic anhydrase inhibitors and prostaglandin analogues. The choice of treatment depends on the effectiveness and side-effects of the drug, co-mobility and cost of treatment. Beta-blockers are one for the first line drug used in treatment of glaucoma but newer medications are increasingly being used as first choice of glaucoma therapy. The exact mechanism of beta-blocker in reducing IOP is not known, but it was suggested that beta-blocker reduces the aqueous humor production by blocking the beta2-receptor on the non-ciliary body epithelium. On average, non-selective beta-blockers such as timolol, levobunolol, carteolol and metipranolol lower the IOP by 20-35% while beta1-receptor antagonist, betaxolol lowers it by 15-25%. However, when the pharmacological therapy is unsuccessful, laser or surgery are required to treat this eye disease (Soltau and Zimmerman, 2002).
The most widely used ocular hypotensive agent is the non-selective beta-blocker, timolol. Timolol is often used as an adjunct therapy to other difference classes of IOP-lowering agents such as brimonidine, travoprost and acetazolamide. In one of the studies, combination therapy of latanoprost and timolol was proved to be more effective in lowering IOP compared to using lataoprost alone in glaucoma treatment (Olander K, 2004). The maleate salt of timolol is soluble in water and alcohol, and has a pKa of approximately 9 in water at 25°C. The current commercially available opthalmic therapies of timolol are timolol maleate topical opthalmic solution and gel-forming ophthalmic solution. Some of the local side effects of topical application of timolol include ocular irritation, burning, pain, itching, erythema and dry eyes. Treating Conditions of the Eye Case Study. Beta-blocker is contra-indicated in patients who have bronchial asthma, history of chronic obstructive pulmonary disease, sinus bradycardia, heart block, or uncontrolled heart failure. In some cases, exacerbation of reactive airways disease and cardiovascular disease due to the systemic absorption of the non-selective beta-blocker has been reported occasionally in patients receiving topical timolol therapy (McEvoy G K, 2002). After long-term usage of timolol, tolerance might develop in some patients. This has been suggested that there is an up-regulation of beta-receptors in target cells in response to constant exposure of antagonist at the beta-receptors (Fechtner, 2008).
1.3 Drug delivery in treatment of glaucoma
There are several approaches in delivering intraocular drugs, among them are topical application, systemic administration, intraocular implants and intravitreal injections. Each of these routes has its own advantages and challenges (Short, 2008). Topical administration is the most widely used route for drug delivery in treating eye diseases. The major challenge of this application to the posterior ocular tissues is poor drug bioavailability resulted from the ocular physiological and anatomical constraints, which include tear fluid turnover rate, nasolacrimal drainage and high efficiency of blood-ocular barrier. It was shown that only 1-5% of the topically applied drugs is absorbed across the cornea and reaches the target intraocular tissues. Furthermore, nasolacrimal drainage contributes to extensive precorneal losses that lead to poor bioavailability. In addition, systemic exposure through nasolacrimal drainage will also cause significant systemic toxicity. Blood-ocular barrier which is located at the retinal pigmented epithelium and the endothelium of the retinal vessels is also a major challenge in delivering topical drugs to the target tissues. This barrier limits the penetration of intraocular drugs to the back of the eyes. Unfortunately, systemically administered drugs are also having the same problem in penetrating the barrier. Hence, alternative drug delivery strategies such as intravitreal injections have been investigated and developed to overcome this problem (Tombrain-Tink and Barnstable, 2006).Treating Conditions of the Eye Case Study.
Intravitreal injection is the administration of intraocular drugs to the vitreous cavity of the eye and this route is becoming increasingly popular in treating glaucoma patients. Due to short half-life of drugs in the vitreous, frequent and repeated injections to the eye are needed to maintain the drug concentration at therapeutic level in the vitreous and the retina. Consequently, this procedure leads to complication such as infection, vitreous hemorrhage, and lens or retinal injury. Sustained release formulation has been developed and possible benefits of particulate drug delivery has been investigated and studied to overcome such complications. The particulate drug delivery systems include microparticles and nanoparticles such as liposome, microcapsule, nanocapsules, microspheres and nanospheres. Liposomes, microcapsules and nanocapsules allow encapsulation of the drug molecules while in microspheres and nanospheres, drugs are dispersed in a spherical polymer matrix. These particulates act as a reservoir to control the release rate during periods of days and sometime even months (Short, 2008; Tombrain-Tink and Barnstable, 2006).
1.4 Microspheres
Microspheres of biodegradable polymers such as poly (lactic-co-glycolic) acid (PLGA) are a combination of drug and polymer. PLGA-based microspheres have several advantages over other controlled released drug delivery system. The administration of these microspheres to the body only requires syringes and needles, thus avoiding surgical implants of controlled-release formulations. Besides that, these PLGA are biodegradable and are biocompatible to the tissues, including the brain tissues (Fournier, 2003). Three microencapsulation techniques are being employed in producing PLGA microspheres these days. Solvent evaporation and solvent extraction process is one of the method which includes single emulsion process and double emulsion process. Treating Conditions of the Eye Case Study. The former process involves oil-in-water emulsification and latter is the most commonly used water-in-oil-in-water (w/o/w) method used to encapsulate water-soluble drugs such as timolol maleate into microspheres. Final emulsions from both processes will undergo solvent removal by extraction or evaporation. The solid microspheres that are produced from these processes will then be filtered or sieved, and finally dried. This technique is widely used because it is easy and does not involve complicated steps. Other methods such as phase separation and spray drying are also being used to encapsulate microspheres. The disadvantage of phase separation is that it needs a careful optimisation of some parameters, such as solvent and polymer type, salt type and concentration in order to obtain any microspheres at all. On the other hand, the limitation of spray drying is that small batches of drug are produced due to loss of product during spray-drying (Jain, 2000).
PLGA, a copolymer of lactic acids and glycolic acids is commonly used in the production of controlled-release biomedical devices such as microparticles and nanoparticles. Incorporation of the active substance in polymer matrix allows drug to be released at a slower rate over a prolonged period, thus reducing the frequency of drug administration and hence improving patient’s compliance. The main target of controlled-release drug delivery is to produce a ‘zero-order’ release pattern, but this was not achieved very often. Some of the small molecules are associated with undesirable initial burst phase during where drugs on the microsphere surface are being released through rapid diffusion, followed by a slow release or no release. During the initial burst phase, excessive release of potent drugs from the polymer for a prolonged time causes severe side effects. However, during the second phase, only a small fraction of drug will be released from the matrix due to decreased driving force in drug depletion (Berkland et al., 2002). In the study conducted by Mao et al. (2007), the effect of different preparation of water-in-oil-in water emulsion on the burst release of fluorescein isothiocyanate labeled dextran from the PLGA microspheres was being investigated. It was found that an increase in drug loading, polyvinyl alcohol concentration and homogenisation speed resulted in a decrease in initial burst. This is due the changes in morphology of the by using different preparation techniques. Treating Conditions of the Eye Case Study.
The main mechanism of drug release from microsphere can be divided to two processes, which are drug diffusion from the polymer network and drug release through polymer degradation. Once PLGA is administered to the eyes, water fills into the network of pore by a negative water gradient and the active compound subsequently diffuses out of the co-polymer. However, this gradient will disappear gradually within a period time and thus the drug molecules are released at a slower rate at a later stage. This process is often coupled with the breakage of ester bonds of the polymer by hydrolysis and it can also be autocatalysed by the accumulation of acidic degradation products and hence leading degradation of PLGA-based microsphere. During this process, oligomers at the surface of microsphere escape from the matrix, leaving behind those who are entrapped inside the matrix core. Size of microsphere plays a very important role in manipulating the rate of degradation. In one of the study, it was shown that larger particle size will degrade more rapidly. This is due to the inner core of the polymer is more acidic compared to its external environment (Grizzi et al. ,1995)
Effect of several factors such as polymer composition and preparation condition on the drug release patterns were being investigated by several studies. It has been demonstrated by Janoria and Mitra (2007) that different lactide/glycolide ratio resulted in different release rate of a lipophilic prodrug (GCV-monobutyrate) from PLGA-based microsphere. PLGA with higher lactide content (65:35) was found to have higher glass transition temperature than lower lactide content (50:50) of PLGA polymer. This was suggested that the former ratio had slower drug diffusion through the polymer matrix, hence longer releasing time.Treating Conditions of the Eye Case Study. On the other hand, an addition of surfactants, polyvinyl alcohol or Triton X-100 to the primary emulsion obtained from the double emulsion solvent evaporation technique resulted in the production of larger particle size, thus slower releasing rate was observed (Bouissou et al., 2006). Besides that, inclusion of additives in the formulation will also affect the release profile of microspheres. Kang F R and Singh J (2001) found out that the addition of PEG 1000 and tricaprin increased the porosity of the PLGA, thus changing its surface characteristics. This has lead to a higher initial releasing rate of bovine serum albumin due to rapid diffusion of the protein through the large pores on the surface of microspheres.
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Different preparation methods effect the morphology and drug distribution of microspheres. A change in the process condition will yield different size distribution and porosity of the microsphere. Some of the critical parameters of determining the microparticle’s morphology are volume ratio of oil to internal water, homogenisation speed and type of solvents used. Surface morphology of microspheres is shown to be influenced by the volume ratio of oil to internal water in a research conducted by Yang et al. (2000). Treating Conditions of the Eye Case Study. An increase in size and initial burst of the microspheres was observed by decreasing the volume ratio from 40:1 to 12:1. More porous microparticles were also observed in lower volume ratio. Homogenisation speed was also proved to be important in determining the morphology of microparticles by Sansdrap and Moes (1993). When homogenisation speed was increased, the microparticulate was found to be smaller. Similarly, different organic phase solvent was proved to produce different size distribution of particles. Song et al. (2006) showed that partially water-soluble solvents such as ethyl acetate and propylene carbonate produced smaller mean particle size compared to the fully water-soluble solvents, acetone and dichloromethane.
Since there are limited studies based on the effect of method parameters on the morphology and drug release profile of timolol maleate encapsulated microsphere, this study aimed to further investigate the effect of volume ratio of oil to internal water, homogenisation speed and type of solvents used. Timolol maleate is encapsulated in PLGA by double-emulsion solvent evaporation method. The surface morphology and particle sizes of the microspheres were being studied using scanning electron microscopy (SEM). On the other hand, the effect on the drug release profile was determined by analysing the released drug sample from the microspheres using ultraviolet spectrophotometer. Treating Conditions of the Eye Case Study.