The relationship between the anterior vitreous interface and the posterior capsule has received increasing attention in the past decade. The advent of integrated intraoperative optical coherence tomography has allowed a real-time opportunity to grasp this dynamic understanding. Here we describe the normal anatomy of this interface in children and then demonstrate the variation in this interface with different forms of pediatric cataract, namely a posterior plaque and posterior capsular opacity due to abnormal adherence to the vitreous face. The authors describe these changes using meticulous annotation. An understanding of these differences will aid the surgeon in managing pediatric cataracts in a more confident and safe manner.

Protocol I, a multicenter randomized clinical trial, compared the visual outcomes of patients treated with 0.5 mg intravitreal ranibizumab with either prompt or deferred (by 24 weeks laser), 4 mg intravitreal triamcinolone with prompt laser, or sham injection with prompt laser for the treatment of center-involving diabetic macular edema (DME). A total of 854 adult patients with type I or II diabetes and any level of non-proliferative diabetic retinopathy or proliferative retinopathy with adequate panretinal photocoagulation, with best-corrected visual acuity (BCVA) of 78 to 24 ETDRS letters (Snellen equivalent of 20/32 to 20/320) and visual loss attributed to macular edema, or retinal thickening with central subfield thickness of at least 250 µm by OCT were enrolled. The main outcomes relevant for practicing clinicians are as follows. (1) Intravitreal ranibizumab treatment provides superior visual outcomes compared to conventional laser treatment. (2) Adjunctive laser treatment does not appear to provide substantial visual benefit compared to ranibizumab treatment alone, but may reduce the number of injections required to resolve DME. Deferral of laser is likely beneficial in patients with worse initial visual acuity. (3) Intravitreal triamcinolone provides similar visual outcomes compared to intravitreal ranibizumab in pseudophakic patients but is associated with a clinically important increased risk of increased intraocular pressure (IOP), need for glaucoma medications, and need for glaucoma surgery. (4) Delayed initiation of intravitreal ranibizumab therapy provides improved visual outcome among patients initially treated with conventional laser photocoagulation or triamcinolone, but the magnitude of the benefit is not as great as is observed when ranibizumab treatment is initiated promptly. (5) The number of ranibizumab injections required to achieve the desired visual outcome decreases substantially after the first year, with the majority of patients not requiring further treatment after 3 years. (6) Patients who do not have a rapid response to ranibizumab still display long-term benefit to continued therapy, although perhaps less than those with immediate improvement. (7) Intravitreal ranibizumab is not only effective in reducing retinal edema and improving BCVA among patients with DME, it is also a disease modifying therapy and induces improvement of the diabetic retinopathy severity score by 2 or more steps in approximately one third of patients. Triamcinolone injection also induces improvement in diabetic retinopathy severity in DME patients, but perhaps to a lesser degree. (8) No increased risk of systemic adverse events was observed among patients treated with intravitreal ranibizumab compared to sham-injected controls or triamcinolone-treated patients, but the low frequency of adverse events, restrictive enrollment criteria, and specific posology employed in this study limit the generalization of this conclusion to patients routinely encountered in clinical practice. (9) There was no clinically important increased risk of major ocular complications among patients treated with intravitreal ranibizumab (including the risk of glaucoma), although endophthalmitis is a potentially devastating outcome should it occur. In addition to the risk of endophthalmitis, intravitreal triamcinolone injection was associated with clinically important increased risk of cataract progression and increased IOP.

The coexistence of cataract and glaucoma represents a challenge for the ophthalmologist and the issue is still open to debate. The surgical management is based on both the visual field defect and the loss of visual acuity. The surgical options currently available are: (1) cataract extraction alone, (2) sequential glaucoma surgery and cataract extraction, and (3) combined surgery by 1 site or by 2 separate sites. Phacoemulsification alone is suggested when glaucoma can be controlled by medication and the visual field defect is moderate and nonprogressive. In case of a refractory glaucoma (3 or more types of medication required) with associated early-stage cataract, phacoemulsification could be postponed until after glaucoma surgery. The cataractogenous effect of the procedure should be considered in this situation. Moreover, cataract extraction performed after a filtering surgery may lead to a reduction of the bleb function. When both glaucoma and cataract are sight impairing, combined surgery is indicated since it allows a greater intraocular pressure decrease than phacoemulsification alone.

Macular edema is most often clinically defined as an accumulation of serous fluid within the neurosensory retina with increased thickness of the central retina. In exudative age-related macular degeneration the leakage of fluid from the choroidal new vessels may be the origin of macular edema. Their abnormal permeability and the inflammatory reaction are mechanisms involved in this accumulation of fluid, which occurs in all layers. Cystoid macular edema is more often associated with subepithelial occult choroidal neovascularization (CNV) than it is with pre-epithelial classic CNV. The simultaneous presence of choroidal new vessels and ME implies a number of cellular dysfunctions especially of Müller cells and subsequently metabolic alterations. The leakage from the choroidal new vessels, predominantly vascular endothelial growth factor (VEGF)-induced, may produce a large accumulation of fluid under the neurosensory retina. It is also likely that the key signaling steps occur prior to the upregulation of VEGF either initiated by, or facilitated by, cytokines, which act under normal basic conditions to counterbalance the integral VEGF effects and, in pathologic circumstances, may either counteract or serve to amplify the process.

Diabetic macular edema (DME), defined as a retinal thickening involving or approaching the center of the macula, represents the most common cause of vision loss in patients affected by diabetes mellitus. In the last few years, many diagnostic tools have proven to be useful in the detection and the monitoring of the features characterizing DME. On the other hand, several therapeutic approaches can now be proposed on the basis of the DME-specific characteristics. The aim of the present chapter is to thoroughly delineate the clinical and morphofunctional characteristics of DME and its current treatment perspectives. The pathogenesis and the course of DME require a complex approach with multidisciplinary intervention both at the systemic and local levels.

Two critical questions one must answer as one applies the results of a clinical trial to clinical practice are: (1) Regardless of whether the trial result is likely to be replicated or reproduced in a second large-scale trial, are the results likely to be reproduced in one's practice? (2) Regardless of whether the experimental treatment was better than the alternative on average for a population of patients, are the results clinically important for a given patient in one's practice? To determine if a study result is likely to be reproduced in one's clinical practice, it may be helpful to answer 5 questions: (1) Have steps been taken to minimize bias? (2) Is the result likely due to the treatment? (3) Is the result unlikely due to chance? (4) Is the study population representative of one's patients? (5) Is the totality of evidence consistent? If the answer to all 5 questions is "yes," then we posit that the trial result is likely to be reproduced in one's practice. If not, the likelihood of reproducibility is low. If the answer is yes to all questions except the last, then reproducibility in one's practice is not clear and depends on the strength of the prior versus the current evidence. If the prior evidence is strong, such as multiple pivotal randomized clinical trials, and if the current trial result is not consistent with the previous studies, then the current result may not be reproduced in one's practice. To determine if a study result is clinically important, a 3-step approach is suggested. Step 1. Decide, a priori, what a clinically meaningful difference between 2 treatments would be. This choice defines regions of beneficial, harmful, and trivial outcomes. Step 2. Identify the confidence intervals (CIs). Determine whether the 95% CI mostly includes the range of clinically beneficial outcomes and lies outside the range of clinically harmful outcomes. If these conditions are met, the result is probably clinically important, but the result may or may not be statistically significant. Put the CIs and the regions of benefit/harm together to make a decision about clinically important effects. Step 3. Assess the proportion of eyes with clinically meaningful changes in vision. The proportion of "responders" among patients receiving a given treatment reflects the likelihood of one's patient having a clinically meaningful response to the treatment. In summary, not all statistically significant results are reproduced, even those of carefully designed clinical trials. Determining if a study result is likely to be reproduced in one's practice is even more problematic. The 5-question test may help in this regard. The 5-question test attempts to assess whether steps have been taken to: minimize bias; avoid confounding; ensure adequate statistical power to support precision in the estimates of population parameters; insure external validity of the trial result; and determine whether there is a convergence of evidence consistent with the trial's major findings. To determine if a statistically significant result is likely to be clinically important, a 3-step approach may be useful, focusing on CIs and the proportion of eyes with clinically meaningful changes in vision. Application of clinical trial results to clinical practice requires critical analysis of the extant literature and good clinical judgment.

Almost 25 years after its introduction, optical coherence tomography (OCT) is still a crucial test in the evaluation of patients affected by diabetic retinopathy. In this chapter, the authors provide an extensive overview of the posterior segment pathological changes induced by diabetes, characterized using OCT. OCT plays a key role in diabetic macular edema (DME) as it assesses related retinal changes both in a qualitative (i.e., DME pattern, presence and aspects of cysts, fluid localization, integrity, and reflectivity of retinal layers) and quantitative (i.e., macula volume, central and sectorial retinal thickness) way, and it is therefore essential for diagnosis, characterization, and follow-up of DME. Diabetic macular ischemia is associated with retinal structural changes which can be investigated using OCT, although its diagnosis relies mostly on fluorescein angiography. Beyond DME and macular ischemia, OCT permits the individuation of many other lesions occurring in the setting of both non-proliferative (i.e., hyperreflective spots, micropseudocysts, hard exudates, microaneurysm, cotton-wool spots) and proliferative (i.e., neovascularization, vitreoschisis, tractional retinal detachment, hemorrhage) retinopathies. OCT provides precious information on several structures, including vitreo-retinal interface, retinal nerve fiber layers, ganglion cell complex, and choroid.

Subconjunctival absorption of aqueous humor is an essential part of glaucoma filtration surgery. Mitomycin C (MMC) and 5-fluorouracil have been used to reduce postoperative episcleral fibrosis and scar formation in the filtering bleb area for more than 2 decades. Both antimetabolites have also been frequently injected before needling revision of failing filtering blebs. Recently, MMC was also tried in tube surgery and nonpenetrating filtering surgery, but its usefulness in these applications has not yet been determined. The main complications and side effects of antimetabolite-enhanced filtration surgery comprise the development of thin-walled cystic blebs, late bleb leaks, bleb infections, endophthalmitis, chronic hypotony, hypotony maculopathy and corneal epithelial toxicity. Besides MMC and 5-fluorouracil, several other agents were proposed for decreasing episcleral healing after glaucoma filtering surgery. Only a few were evaluated in randomized clinical trials, and none became generally accepted or widely used.

Optical coherence tomography angiography (OCT-A) is a promising new method for visualizing the retinal vasculature and choroidal vascular layers in the macular area and provides depth-resolved functional information on blood flow in these vessels. OCT-A is based on the concept that in a static eye the only moving structure in the fundus of the eye is blood flowing through the vessels. Contrast is generated based on the difference between moving cells in the vasculature and the static surrounding tissue. Artifacts can arise due to scan positioning errors caused by normal ocular microsaccades. In order to avoid artifacts, a sequence of OCT B-scans in the exact same retinal location must be taken to detect flow. Active eye-tracking (TruTrack™) using the simultaneous acquisition of fundus and optical coherence tomography (OCT) images presents a very reliable method of acquiring OCT volume scans without motion artifacts and helps significantly improve signal-to-noise ratio. This system also allows the use of a full spectrum amplitude decorrelation algorithm that produces clear differentiation between blood flow and static tissue without sacrificing the axial resolution of OCT images. Accuracy in layer segmentation, which requires high-resolution OCT B-scans, is crucial for producing reliable OCT-A images. This can be achieved through automated or manual layer segmentation. During OCT scan acquisition, the effect of axial motion (e.g. a patient moving towards the camera) is compensated for by geometric alignment of successive B-scans before analyzing temporal changes.

This chapter describes the techniques and pitfalls that the reader may come across when dealing with complex pediatric cataract cases. Each eye in these circumstances is unique, and the examples and general advice shared are intended to help the reader develop a plan for surgery and a road map to avoid potential problems. As in all types of surgery, careful planning is essential. The old saying 'Fail to prepare, then you prepare to fail' is no more true than when dealing with children who have complex cataract. In this chapter, the following circumstances where pediatric cataract may be seen are discussed: retinoblastoma, retinopathy of prematurity, lenticonus, congenital rubella syndrome, trauma, microcornea, pediatric uveitis, Hallermann-Streiff syndrome, Stickler syndrome, Lowe syndrome, subluxated lens, and after previous intraocular surgery (glaucoma, keratoplasty).