The tenth volume of Recent Advances in Ophthalmology contains some selected chapters on cornea, uvea, secondary glaucoma, lens, retina, oculoplastic surgery, and neuro-ophthalmic disorders. First time in the serial publication, three editorials—artificial cornea, diabetic retinopathy, and endophthalmitis are included to provide an over view of the problem to the readers.

Besides editorial on artificial cornea, five articles are included on cornea. Sinha and coauthors have described corneal dystrophies in great detail covering prevalence, international classification, inheritance, histopathology, clinical features and treatment.

More and more cases of keratoconus are being diagnosed with the introduction of newer technology. Padmanabhan and Gupta have elaborated the management of keratoconus including sclera lens, collagen cross-linking, intracorneal ring segments, deep anterior lamellar keratoplasty and penetrating keratoplasty. It is reported that collagen cross-linking results in significant improvements in astigmatism, visual acuity and keratometry readings. There is an ample evidence to suggest that the collagen-cross-linking can stabilize the progression of keratoconus if not an actual improvement in the severity of the condition.

Historically, lamellar keratoplasty was the first technique of corneal transplantation. However, it was replaced by penetrating keratoplasty due to reduced optical clarity consequent to irregularities of stromal bed. Recently, there is re-emergence of lamellar keratoplasty. DALK is a new technique in which opaque corneal tissue is removed to the level of Descemet membrane. The technique is so much improved that the visual outcome is comparable or even better than that of penetrating keratoplasty. Gupta and Padmanabhan described the surgical steps of DALK with the help of colored photographs.

If vision cannot be restored by PK in cases of corneal blindness, keratoprosthesis or artificial cornea may be implanted in such patients for visual improvement. Two types of keratoprostheses—Pintucci biointegrated and Dohlman keratoprostheses are—available for this purpose. Maskati presented a pictorial description of implantation of keratoprosthesis.9

Multiple ophthalmic equipment are presently available for diagnostic purpose. Pentacam is a single diagnostic tool that can imagine the entire anterior segment of the eye and present the data in an easy-to-interpret form. Shetty and Shetty briefly discussed the use of instrument with the help of multiple illustrations.

In spite of remarkable advances in the field of uveitis, the etiological diagnosis of the disease poses considerable problems. Biswas and his group stressed the importance of PCR in intraocular inflammations. They have also reviewed the recent treatment of posterior uveitis for the benefit of readers.

In the present volume, interesting topics on secondary glaucoma such as pigmentary glaucoma, exfoliative glaucoma, and epidemic dropsy glaucoma are included. Both pigmentary glaucoma and exfoliative glaucoma are described in some details covering etiology and pathogenesis.

The correct calculation of intraocular lens power has always worried the cataract surgeon. The ultimate goal of IOL implantation is to achieve emmetropia. Its importance increases especially when accommodative or phakic lenses are implanted. Various formulas for IOL power calculation are summarized by Garg. Rajan and coworkers reviewed the recent development in the manufacturing materials and designs of new IOLs including multifocal and accommodative lenses.

Diabetic macular edema is a common cause of visual loss from diabetic retinopathy. Results of Visual Function Questionnaire suggest that it can adversely affect the quality of life of the patients greater than those suffering from glaucoma and cataract. Youssef and Chandra have discussed the pathogenesis and treatment options of diabetic macular edema concisely.

The editorial and chapter on endophthalmitis have adequately covered the subject. Chapters on ocular surface reconstruction and ptosis represent the advances in ocular plastic surgery. Our understanding of multiple sclerosis, migraine and nystagmus is not advanced to a desired level although they are common and important disorders of neuro-ophthalmology.

Recent advances in ophthalmology have considerably improved the quality of medical and surgical management of the patients with eye diseases. Hopefully, the postgraduate students in ophthalmology and general ophthalmic practitioners will find the present volume helpful not only in the basic understanding of new developments in the subject but also in day-to-day clinical practice and care of the patients.

We wish to record our thanks to Dr Rajesh Sinha for reviewing some chapters of RAO.

Shri Jitendar P Vij (Chairman and Managing Director), Jaypee Brothers Medical Publishers (P) Ltd. and staff especially Mr Tarun Duneja (Director-Publishing) deserve our sincere thanks for their continued interest in the publication of the Recent Advances in Ophthalmology Series.

Eyes with dense vascularization, keratinization, and desiccation create a hostile environment that spells disaster for an attempted graft. Eyes with chemical injuries, Stevens-Johnson syndrome, and neurotrophic scars typically fall into this category. Immunologically-mediated graft rejections continue to be the major cause of graft failure.

All these factors have driven the search for an artificial cornea. Currently the term Artificial Cornea refers to 2 types of artificial replacement – Keratoprosthesis and Tissue-Engineered corneal equivalents.

Fully synthetic keratoprosthesis like the Boston KPro are designed to replace the central portion of an opaque cornea. The concept of a core-and-skirt device in which a biointegrable skirt surrounds a central optic led to the Chirilia keratoprosthesis, and later its modification, the AlphaCor. The Pintucci keratoprosthesis is another device designed on the core-and-skirt principle. Maskati has nicely described the surgical technique of keratoprosthesis with the help of multiple illustrations in Chapter 5. The OOKP designed by Strampelli, was modified by Falcinelli uses an osteo-odonto-alveolar lamina into which an optical PMMA cylinder of appropriate dioptric power is cemented. After remaining implanted in a subcutaneous pouch created in the cheek for 3 months, it is implanted in the eye which would have had a buccal mucosal graft done earlier in preparation for the implant.

All these devices have had varying degrees of success in well-selected patients but have also had their share of problems and complications. Apart from the complexities of the surgery itself, sometimes involving multiple stages, serious postoperative complications like extrusion, retroprosthetic membranes, calcification, infection, glaucoma, and retinal detachment have been its major drawbacks. Because of the high risk of complications, this surgery is usually reserved as a last resort in patients with bilateral end stage Ocular Surface Disease who are unsuitable for allografting.12

The coalition of material science and cell biology has been responsible for the blossoming of an innovative approach called Tissue engineering, which combines living cells with a wide range of selected biomaterials to repair, replace or restore tissue function. The tissue engineering for 2-dimensional organization of tissues like the skin is relatively easy, but the 3-D tissues like the multilayered cornea poses some challenges. Combining tissue engineering with stem cell technology and nanotechnology may pave the way to recreate corneas de novo, mimicking their complex architecture and specialized properties and serving their multifaceted function. Several biomimetic natural polymers have been used as stromal substitutes, collagens being the most favored. Its biocompatibility, low toxicity, structural and immunological properties meet the desired requirements of a scaffold and its use for the skin and cartilage are well documented. Its mechanical integrity and stability have been strengthened by chemical cross-linking. Collagen types I and III are now available from recombinant sources and, therefore, alleviate the risk of transmission of infectious agents from animal sources and are also less likely to cause immunological or allergic reactions.

A Phase I clinical trial of implanting a 3-D scaffold of cross-linked recombinant human collagen as an extracellular matrix in 10 patients who underwent anterior lamellar keratoplasty, showed a seamless biointegration of the implant into the host tissue. The biosynthetic implants remained stably integrated and avascular for 2 years after surgery. Corneal reepithelialization and nerve regeneration restored a morphologically normal epithelium and ocular surface that supported an adequate tear film. This itself is a major achievement that heralds the dawn of a new era in Regenerative Medicine. The next challenge would be to create a full thickness functional human corneal construct, with the same transparency, tensile strength and regenerative potential as the natural cornea. The low proliferative index of the human corneal endothelium makes this difficult at the present time.

In the future, tissue engineered matrices may be produced either fully furnished with living cells ready for implantation or packaged as sterile, non-cytotoxic matrices that become functional by ingrowth of cells and nerves from the adjacent host tissue.

Their biointegration and biocompatibility, their biomechanical and optical similarity to normal corneal tissue, and their permeability to nutrients and drugs would make them the ideal alternative to human donor tissue in the future. In addition, they would form a model for biological and pharmacotoxicity testing and more excitingly for gene therapy.

Diabetic retinopathy is primarily a microvascular disease, characterized by thickening of basement membrane of the capillaries, increased permeability and occlusion, resulting in visual loss through macular edema (DME) and proliferative disease (PDR). The gold standard of treatment for these visual complications is laser photocoagulation, focal and scatter pattern respectively. Vitrectomy is reserved for the advanced stages of PDR, i.e. vitreous hemorrhage and tractional retinal detachment. Establishment of inflammatory basis of DR marked a paradigm shift in understanding and management of DR, and heralded the introduction of intravitreal corticosteroids, mainly for the management of DME, resulting in promising, though modest and transient visual gains. Intravitreal triamcinolone still retains utility in the treatment of DME refractory to laser treatment. With renewed interest in molecular basis of diabetic retinopathy, particularly the role of vascular endothelial growth factor (VEGF), another paradigm shift occurred in the management of DR: use of intraocular anti-VEGF agents, for treatment of both PDR and DME. Three drugs have been most popular with researchers and clinical practitioners: ranibizumab, bevacizumab and pegaptanib sodium. In a recent trial by Diabetic Retinopathy Clinical Research Network (DRCR), ranibizumab has been demonstrated as the first pharmacotherapeutic alternative to surpass the effects of laser photocoagulation for DME, both in terms of visual gain and prevention of visual loss.₇ Need for repeated injections have been the bane of all the existing pharmacotherapies, leading to increased complications as well as exorbitant costs, when compared to photocoagulation. With typical resilience, researchers have now focused attention on long-acting depot preparations of the various therapeutic agents as well as topical agents delivered as eye drops. Simultaneously, others are looking at retinal repair using stem cells in DR and candidate genes for DR through genome-wide association studies.

While the future indeed looks promising for the arrival of new therapeutic agents which would improve the modest but stable outcome with lasers in early DR, a reality 14check of evidence-based treatments in DR reconfirmed the old wisdom: photocoagulation and vitrectomy remain the most evidence-backed treatments of DR; while control of systemic disease remains the cornerstone of primary prevention. It is noteworthy that the systemic control in diabetes refers to other closely related systemic diseases as well, which significantly and adversely affect the course of ocular disease as well: particularly, hypertension, nephropathy and dyslipidemia.

The National Eye Institute, Bethesda, USA has supported various trials (DRS, ETDRS. DRVS) and has established that laser treatment is beneficial for diabetic retinopathy and vitreous surgery may be beneficial in some. It has been proved by well controlled research studies such as Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), Diabetes Control and Complications Trial (DCCT), and United Kingdom Prospective Diabetes Study (UKPDS) that intense control of hyperglycemia, control of high blood pressure and lipid control have positive and beneficial effect on prevention/postpone/progression of diabetic retinopathy and recent published reports are supportive of this fact. It is also observed recently that the need for laser treatment for diabetes macular edema for type II diabetes mellitus has come down to 43% (2001–2006), though the prevalence of diabetes mellitus has dramatically increased. Nevertheless the diabetic macular edema (DME) remains by far the most common cause of vision loss. The vision loss by DME on quality of life can have greater effect than those seen in patients with glaucoma and cataract. Youssef and Suresh Chandra have comprehensively described the management of macular edema in Chapter 14 and emphasized that it is necessary to manage it in a more effective manner.

Recently, ACCORD study reported that treatment of dyslipidemia in DM with fenofibrate and statins resulted in 40% reduction in progression of DR. Similarly, rosiglitazones for treatment of systemic diabetes have been shown to delay onset of PDR, though sporadic association with DME has to be monitored for.

While we await the future treatment modalities like inhibition of angiogenic factors as well as regenerative, genetic and topical therapies, we can optimize diabetic care here and now by early identification of patients with DM and DR through proactive door-to-door surveys, improving the patients’ access to eye care by screening for sight-threatening DR using new technologies like telemedicine, educating the diabetic patients about the importance of examination and follow-up of diabetic eyes from pre-retinopathy stages, and a holistic approach to the patient with DR by taking a comprehensive care of systemic diabetes as well as related diseases.

According to WHO, 41.9 million people were affected by diabetes in India. This figure is estimated to rise to 79.4 million by 2030, the largest population of any nation in the world. As per the recent epidemiological survey conducted at Aravind Eye Hospital, Theni has shown that there are 47.8 million of diabetics in India. The estimated population of diabetic retinopathy is 5.8 million. Against this background, successful strategies have to be developed to address the above mentioned problems to prevent blindness due to diabetic retinopathy in India. It is well known that only about 17 to 20% of diabetic people will have diabetic retinopathy and need active intervention by the trained ophthalmologists and the rest of them will be having normal fundus with good vision and no retinopathy and need only a periodical follow up by the diabetologists and the ophthalmologists as a team.15

Our objective must be to retain the presenting vision of majority of the people throughout their lifetime and we should aim at reducing the number of diabetics who will require lasers and vitrectomy and also to retain the good prevailing vision of all the diabetics by early detection and proper comprehensive quality management of every diabetic patient.

The challenges lie not only in creating awareness amongst the lay public but also in the health professionals, that persons with diabetes must undergo a detailed eye examination and that it has to be done periodically as advised. A systematic approach to health education and creating awareness among patients and various health personnel and matching it with appropriate screening and service delivery mechanisms will go a long way in preventing blindness due to diabetic retinopathy.

There are two forms of endophthalmitis: exogenous and endogenous. The latter is less common (5–10%) and develops secondary to hematogenous spread from an infective focus anywhere in the body. Exogenous endophthalmitis after cataract surgery is by far the most frequent (90%). It is a matter of great concern that the rate of endophthalmitis following cataract surgery has increased from 0.09% during the 1990s to 0.27% in 2000. The greater use of clear corneal incision may be one of the reasons for this rise. Endophthalmitis can also complicate penetrating keratoplasty, glaucoma filtration surgery, pars plana vitrectomy, and even minor procedures like intravitreal injections. The incidence of posttraumatic endophthalmitis is high especially with open globe injury or retained intraocular foreign body.

Both immunosuppressive disorders and major surgical procedures facilitating the chances of blood-borne infections are considered risk factors for the development of endophthalmitis. The infecting organisms vary with geographic location, and long-term use of antibiotics and steroids. Gram-positive bacteria are responsible for most cases of postoperative endophthalmitis in the Europe and US; they cause less severe disease compared with Gram-negative organisms. In East Asia, Gram-negative organisms, especially Klebsiella accounts for most cases of endophthalmitis. Streptococcal infection causes an early onset severe endophthalmitis with poor outcome. Fungal endophthalmitis is predominantly caused by Candida albicans, Aspergillus, and Fusarium sp. Candida infection presents a classical fundus picture consisting of localized fluffy creamy-white retinal nodules associated with vitreous opacities (like string of pearls) and haze.

Timely microbiological evaluation of cases of endophthalmitis is important for their management. Hence, it is important that every ophthalmologist builds a system where specimens can be transferred to a laboratory and processed within one hour of collection rather than being kept in a refrigerator for several hours to days before being processed. Where facilities are not available, at least a liquid transport medium should be available for immediate inoculation.

The prognosis of endophthalmitis is often poor unless diagnosed early and managed aggressively. There is a need to reemphasize the concept “Prevention is better than cure” to eliminate the risk of intraocular contamination by ensuring proper asepsis and sterility at the time of ocular surgery. The role of prophylactic antibiotic preceding surgery, addition of antibiotics in the infusion line and subconjunctival antibiotic therapy at the end of surgery remains controversial. Recently, intracameral 18use of moxifloxacin is recommended in the prophylaxis of endophthalmitis. The European Society of Cataract and Refractive Surgeons Endophthalmitis Study (ESCRS) reported that prophylactic use of intracameral antibiotic reduces the incidence of postoperative endophthalmitis after cataract surgery by 75%.

Management of exogenous endophthalmitis mainly consists of intravenous antimicrobial agents and pars plana vitrectomy. The urgency to treat endophthalmitis should also be emphasized since every hour of delay in administration of intravitreal antibiotic could make a significant difference in the outcome, especially in case of infection with virulent organism such as Pseudomonas, Bacillus species. Intravitreal vancomycin, cefuroxime or amikacin are the mainstay of treatment of endophthalmitis from the time of the Endophthalmitis Vitrectomy Study.

Administration of systemic antibiotics forms sheet anchor for the management of endogenous endophthalmitis but it does not provide any additional benefit in acute or subacute exogenous endophthalmitis. The use of intravitreal or systemic corticosteroids in the treatment of endophthalmitis is controversial.

Pars plana vitrectomy has several added advantages when performed for managing exogenous endophthalmitis. It results in reduction of inflammatory materials, pathogens and toxins, and improves the chances of obtaining better vision. Additionally, vitrectomy offers samples for culture and sensitivity. The role of vitrectomy in endogenous endophthalmitis is not well defined.

A significant percentage of cases of endogenous endophthalmitis are caused by fungi; most common being Candida. The fungal infection can be controlled by systemic and intravitreal therapy. The current protocol of treatment includes amphotericin B (5–10 μg/0.1 mL) and fluconazole. These drugs may not control infection in all cases. Recently, a second generation triazole, voriconazole, is introduced that is more safe and effective and can be administered systemically as well as intravitreally. Common fungi like Candida, Aspergillus, and Fusarium are very susceptible to voriconazole. Vitrectomy combined with intravitreal therapy is indicated in cases of endogenous fungal endophthalmitis associated with moderate to severe vitritis.

Saxena and Sharma have presented concise and up-to-date information on the diagnosis and management of endophthalmitis in Chapter 15.