Advances in the Management of Keratoconus: Evolving Paradigms in Inflammatory Pathogenesis and Pediatric Care

Abstract

Clinicians have traditionally classified keratoconus (KC), a progressive, asymmetric corneal ectasia, as a strictly noninflammatory condition. Today, however, modern proteomic and transcriptomic analyses have completely catalyzed a paradigm shift, exposing a highly complex inflammatory pathogenesis. Concurrently, advancements in tissue engineering, photochemical cross-linking (CXL), and optical rehabilitation have fundamentally transformed how we manage the disease across all demographics. The objective of this study was to review our evolving understanding of KC pathogenesis, with a specific focus on inflammatory mediators and emerging pharmacological adjuncts like trehalose. In addition, this review evaluates the latest evidence regarding specialty contact lenses, pediatric and adult CXL protocols, and the expanding role of tissue addition keratoplasties. We conducted a comprehensive review of recent literature (2023–2025) evaluating tear film cytokines, wavefront-guided (WFG) scleral lenses (SLs), customized CXL (C-CXL), and novel allogeneic surgical interventions. Tear film analyses consistently demonstrate a persistent upregulation of pro-inflammatory cytokines in KC patients. On the rehabilitation front, WFG SLs have rapidly become the standard for managing higher-order aberrations while simultaneously protecting the cornea against mechanical microtrauma. Surgically, adult CXL is evolving toward highly customized, topography-guided protocols, whereas pediatric KC still demands prompt, standard epithelium-off intervention. For advanced disease, corneal allogenic intrastromal ring segments, stromal lenticule addition keratoplasty, and Bowman’s layer transplantation now offer highly biocompatible, tissue-additive alternatives that significantly delay the need for penetrating keratoplasty. KC management is actively transitioning from reactive mechanical stabilization to proactive, biologically informed strategies. Recognizing KC as an inflammatory-mediated ectasia opens the door to novel pharmacological therapies, while advanced SLs, C-CXL, and allogeneic tissue addition are providing patients with unprecedented visual rehabilitation and structural preservation.