from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.lib.colors import HexColor, white, black
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether
)
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.platypus import PageBreak

OUTPUT = "/tmp/workspace/steroids-ophthalmology/Steroids_in_Ophthalmology_MS_Exam.pdf"

# Colors
DARK_BLUE = HexColor("#1a3a5c")
MID_BLUE = HexColor("#2e6da4")
LIGHT_BLUE = HexColor("#d6e8f7")
ACCENT = HexColor("#e8f0fb")
GOLD = HexColor("#b8860b")
RED = HexColor("#c0392b")
GREEN = HexColor("#1a7a4a")
LIGHT_GRAY = HexColor("#f4f4f4")
BOX_BORDER = HexColor("#2e6da4")
ORANGE = HexColor("#d35400")

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=2*cm, rightMargin=2*cm,
    topMargin=2.2*cm, bottomMargin=2.2*cm
)

styles = getSampleStyleSheet()

# Custom styles
title_style = ParagraphStyle(
    "Title", parent=styles["Title"],
    fontSize=22, textColor=white,
    alignment=TA_CENTER, spaceAfter=4, fontName="Helvetica-Bold"
)
subtitle_style = ParagraphStyle(
    "Subtitle", parent=styles["Normal"],
    fontSize=12, textColor=white,
    alignment=TA_CENTER, spaceAfter=2, fontName="Helvetica"
)
h1_style = ParagraphStyle(
    "H1", parent=styles["Heading1"],
    fontSize=14, textColor=white,
    spaceAfter=6, spaceBefore=12, fontName="Helvetica-Bold",
    leftIndent=0, borderPadding=(5, 8, 5, 8)
)
h2_style = ParagraphStyle(
    "H2", parent=styles["Heading2"],
    fontSize=12, textColor=DARK_BLUE,
    spaceAfter=4, spaceBefore=8, fontName="Helvetica-Bold",
    borderPadding=2
)
h3_style = ParagraphStyle(
    "H3", parent=styles["Heading3"],
    fontSize=11, textColor=MID_BLUE,
    spaceAfter=3, spaceBefore=6, fontName="Helvetica-Bold"
)
body_style = ParagraphStyle(
    "Body", parent=styles["Normal"],
    fontSize=10, textColor=black,
    spaceAfter=4, spaceBefore=2,
    leading=14, alignment=TA_JUSTIFY, fontName="Helvetica"
)
bullet_style = ParagraphStyle(
    "Bullet", parent=styles["Normal"],
    fontSize=10, textColor=black,
    spaceAfter=3, spaceBefore=1,
    leading=14, fontName="Helvetica",
    leftIndent=14, bulletIndent=4
)
note_style = ParagraphStyle(
    "Note", parent=styles["Normal"],
    fontSize=9.5, textColor=HexColor("#444444"),
    spaceAfter=3, spaceBefore=2,
    leading=13, fontName="Helvetica-Oblique",
    leftIndent=10
)
source_style = ParagraphStyle(
    "Source", parent=styles["Normal"],
    fontSize=8.5, textColor=HexColor("#666666"),
    spaceAfter=2, spaceBefore=1,
    leading=12, fontName="Helvetica-Oblique"
)
warning_style = ParagraphStyle(
    "Warning", parent=styles["Normal"],
    fontSize=10, textColor=RED,
    spaceAfter=3, spaceBefore=2,
    leading=14, fontName="Helvetica-Bold"
)


def section_header(text, color=DARK_BLUE):
    """Creates a colored section header box."""
    data = [[Paragraph(text, h1_style)]]
    t = Table(data, colWidths=[17*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0, 0), (-1, -1), color),
        ("TOPPADDING", (0, 0), (-1, -1), 8),
        ("BOTTOMPADDING", (0, 0), (-1, -1), 8),
        ("LEFTPADDING", (0, 0), (-1, -1), 10),
        ("RIGHTPADDING", (0, 0), (-1, -1), 10),
        ("ROUNDEDCORNERS", [4, 4, 4, 4]),
    ]))
    return t


def two_col_table(headers, rows, col_widths=None):
    """Makes a styled two-column table."""
    if col_widths is None:
        col_widths = [6*cm, 11*cm]
    data = [[Paragraph(h, ParagraphStyle("TH", parent=styles["Normal"],
                        fontSize=10, fontName="Helvetica-Bold",
                        textColor=white)) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), ParagraphStyle("TD", parent=styles["Normal"],
                        fontSize=9.5, fontName="Helvetica", leading=13)) for c in row])
    t = Table(data, colWidths=col_widths)
    t.setStyle(TableStyle([
        ("BACKGROUND", (0, 0), (-1, 0), DARK_BLUE),
        ("BACKGROUND", (0, 1), (-1, -1), LIGHT_GRAY),
        ("ROWBACKGROUNDS", (0, 1), (-1, -1), [white, LIGHT_GRAY]),
        ("GRID", (0, 0), (-1, -1), 0.5, HexColor("#cccccc")),
        ("TOPPADDING", (0, 0), (-1, -1), 6),
        ("BOTTOMPADDING", (0, 0), (-1, -1), 6),
        ("LEFTPADDING", (0, 0), (-1, -1), 8),
        ("RIGHTPADDING", (0, 0), (-1, -1), 8),
        ("VALIGN", (0, 0), (-1, -1), "TOP"),
    ]))
    return t


def info_box(title, content_paras, bg=LIGHT_BLUE, border_color=BOX_BORDER):
    """Creates a colored info box with title."""
    rows = [[Paragraph(f"<b>{title}</b>", ParagraphStyle("BoxTitle", parent=styles["Normal"],
                       fontSize=10, fontName="Helvetica-Bold", textColor=DARK_BLUE))]]
    for p in content_paras:
        rows.append([p])
    t = Table(rows, colWidths=[16.5*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0, 0), (-1, 0), LIGHT_BLUE),
        ("BACKGROUND", (0, 1), (-1, -1), ACCENT),
        ("BOX", (0, 0), (-1, -1), 1, border_color),
        ("LINEBELOW", (0, 0), (-1, 0), 1, border_color),
        ("TOPPADDING", (0, 0), (-1, -1), 6),
        ("BOTTOMPADDING", (0, 0), (-1, -1), 6),
        ("LEFTPADDING", (0, 0), (-1, -1), 10),
        ("RIGHTPADDING", (0, 0), (-1, -1), 10),
    ]))
    return t


# ============================================================
# BUILD CONTENT
# ============================================================
story = []

# === COVER HEADER ===
cover_data = [[
    Paragraph("STEROIDS IN OPHTHALMOLOGY", title_style),
    Paragraph("Effects on the Eye & Other Systems | Indications | Side Effects", subtitle_style),
    Paragraph("MS Ophthalmology Examination — 20 Marks", subtitle_style),
    Paragraph("Sources: Goodman &amp; Gilman's Pharmacology · Kanski's Clinical Ophthalmology · Wills Eye Manual · Scott-Brown's · Family Medicine", subtitle_style),
]]
cover = Table(cover_data, colWidths=[17*cm])
cover.setStyle(TableStyle([
    ("BACKGROUND", (0, 0), (-1, -1), DARK_BLUE),
    ("TOPPADDING", (0, 0), (-1, -1), 18),
    ("BOTTOMPADDING", (0, 0), (-1, -1), 18),
    ("LEFTPADDING", (0, 0), (-1, -1), 12),
    ("RIGHTPADDING", (0, 0), (-1, -1), 12),
]))
story.append(cover)
story.append(Spacer(1, 0.5*cm))

# ============================================================
# SECTION 1: INTRODUCTION
# ============================================================
story.append(section_header("1. INTRODUCTION TO STEROIDS IN OPHTHALMOLOGY", DARK_BLUE))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph(
    "Glucocorticoids (corticosteroids) are among the most widely used therapeutic agents in ophthalmology. "
    "They exert potent anti-inflammatory, immunosuppressive, and anti-proliferative effects by binding to "
    "intracellular glucocorticoid receptors, leading to modulation of gene transcription. In ophthalmology, "
    "they are available in multiple formulations including topical drops/ointments, periocular injections, "
    "intravitreal implants, and systemic preparations.",
    body_style
))
story.append(Paragraph(
    "Commonly used ophthalmic steroids include: <b>Dexamethasone</b>, <b>Prednisolone acetate</b>, "
    "<b>Fluorometholone</b>, <b>Loteprednol etabonate</b>, <b>Difluprednate</b>, and <b>Triamcinolone acetonide</b>.",
    body_style
))
story.append(Spacer(1, 0.2*cm))

# ============================================================
# SECTION 2: INDICATIONS
# ============================================================
story.append(section_header("2. INDICATIONS FOR STEROIDS IN OPHTHALMOLOGY", MID_BLUE))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("2.1 Topical / Local Indications", h2_style))

indications_table = two_col_table(
    ["Condition", "Rationale / Notes"],
    [
        ["Anterior uveitis (iritis/iridocyclitis)", "Reduces anterior segment inflammation; prevent posterior synechiae"],
        ["Allergic conjunctivitis & vernal keratoconjunctivitis", "Fluorometholone or loteprednol preferred to minimize IOP risk"],
        ["Giant papillary conjunctivitis", "Reduces papillary hypertrophy and mast cell degranulation"],
        ["Episcleritis / scleritis", "Topical for episcleritis; systemic often needed for scleritis"],
        ["Keratitis (non-infectious / immune)", "Stromal keratitis, interstitial keratitis, phlyctenular keratitis"],
        ["Marginal corneal ulcer", "Hypersensitivity to Staphylococcal exotoxins; short course"],
        ["Postoperative inflammation", "After cataract, refractive, glaucoma filtering, and corneal surgery"],
        ["Ocular burns (chemical/thermal)", "Limits inflammatory cascade; used with caution re: melting"],
        ["Corneal graft rejection prophylaxis", "Long-term topical post-penetrating keratoplasty"],
        ["Cicatricial pemphigoid (ocular)", "Topical and systemic combined approach"],
        ["Dry eye syndrome (severe inflammatory)", "Short-term; loteprednol preferred"],
    ],
    col_widths=[6.5*cm, 10.5*cm]
)
story.append(indications_table)
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("2.2 Periocular / Intravitreal Indications", h2_style))
story.append(Paragraph(
    "Posterior sub-Tenon's capsule injection and intravitreal routes are used when higher intraocular "
    "drug concentrations are required:", body_style
))
for item in [
    "Posterior uveitis (sub-Tenon's triamcinolone or systemic)",
    "Cystoid macular edema (CME) — diabetic, post-surgical, uveitic",
    "Diabetic macular edema (intravitreal dexamethasone implant, fluocinolone implant)",
    "Sympathetic ophthalmia",
    "Visualization during vitrectomy (intravitreal triamcinolone — marks vitreous)",
    "Macular edema secondary to retinal vein occlusion",
    "Chronic non-infectious uveitis (fluocinolone acetonide or dexamethasone sustained-release implant)",
]:
    story.append(Paragraph(f"• {item}", bullet_style))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("2.3 Systemic Indications", h2_style))
for item in [
    "Optic neuritis — IV methylprednisolone pulse followed by oral taper (speeds visual recovery, does NOT improve final VA)",
    "Arteritic anterior ischemic optic neuropathy (GCA) — high-dose IV steroids; prevent fellow eye involvement",
    "Orbital inflammatory disease (orbital pseudotumor, thyroid eye disease — active phase)",
    "Sympathetic ophthalmia",
    "Severe ocular cicatricial pemphigoid",
    "Vogt-Koyanagi-Harada (VKH) disease",
    "Severe posterior uveitis / panuveitis",
    "Post-surgical inflammation unresponsive to topical therapy",
    "Ocular manifestations of systemic vasculitis (e.g., Wegener's, PAN)",
]:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Spacer(1, 0.3*cm))
story.append(info_box(
    "CLINICAL PEARL — Route-specific formulations (Goodman & Gilman)",
    [
        Paragraph("Dexamethasone 0.1% — steroid-responsive inflammatory conditions of the conjunctiva, cornea, anterior segment, and postoperative inflammation.", note_style),
        Paragraph("Difluprednate 0.05% emulsion — ocular pain; postoperative ocular inflammation; uveitis.", note_style),
        Paragraph("Fluorometholone 0.1–0.25% — allergic conjunctivitis; vernal KC; keratitis; burns; postoperative inflammation; uveitis.", note_style),
        Paragraph("Loteprednol etabonate 0.2–0.5% — allergic conjunctivitis; iritis; cyclitis; keratitis; postoperative inflammation. Metabolized to inactive compounds — LOWEST risk of IOP elevation.", note_style),
        Paragraph("Prednisolone acetate 1% — bacterial conjunctivitis; anterior segment inflammation; burns; herpes zoster ophthalmicus; uveitis.", note_style),
    ]
))

story.append(Spacer(1, 0.3*cm))

# ============================================================
# SECTION 3: OCULAR EFFECTS / SIDE EFFECTS
# ============================================================
story.append(section_header("3. EFFECTS OF STEROIDS ON THE EYE", ORANGE))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph(
    "Steroids exert both therapeutic and adverse effects on ocular structures. Understanding these is "
    "fundamental for safe clinical practice.", body_style
))

# 3.1 GLAUCOMA
story.append(Paragraph("3.1 Steroid-Induced (Steroid-Response) Glaucoma", h2_style))
story.append(Paragraph(
    "<b>Mechanism:</b> Steroids reduce the outflow facility of the trabecular meshwork (TM) by increasing "
    "deposition of extracellular matrix in the TM, reducing phagocytic activity of TM cells, and "
    "upregulating myocilin (MYOC) gene expression — all of which impede aqueous humor outflow, "
    "resulting in elevated intraocular pressure (IOP).",
    body_style
))
story.append(Paragraph(
    "<b>Onset:</b> Typically 2–4 weeks after starting ocular (topical, periocular, intravitreal) steroids. "
    "Rarely, an acute IOP rise occurs within hours with systemic IV administration.",
    body_style
))
story.append(Paragraph(
    "<b>Risk factors for steroid response:</b>",
    body_style
))
for item in [
    "Primary open-angle glaucoma (POAG) or family history of glaucoma",
    "Ocular trauma",
    "Diabetes mellitus",
    "High myopia",
    "African descent",
    "Young age (children are particularly susceptible)",
]:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Paragraph(
    "<b>Prevalence:</b> In the absence of a family history of open-angle glaucoma, only about 5% of "
    "normal individuals show a marked IOP increase. With a positive family history, moderate-to-marked "
    "IOP elevations may occur in up to 90% of patients.",
    body_style
))
story.append(Paragraph(
    "<b>Route of risk (most to least):</b> Intravitreal &gt; periocular injection &gt; topical &gt; oral &gt; inhaled/nasal/dermatological",
    body_style
))
story.append(Paragraph(
    "<b>Potency of IOP rise:</b> More potent steroids (dexamethasone, difluprednate) cause greater IOP rises "
    "compared to weaker steroids (fluorometholone, loteprednol). "
    "Loteprednol was specifically designed to reduce (but not eliminate) IOP risk.",
    body_style
))
story.append(Paragraph(
    "<b>Reversal:</b> IOP typically returns to pretreatment levels after stopping steroids. When IOP elevation is severe, "
    "it may persist for months. Loteprednol has the best safety profile.",
    body_style
))
story.append(Paragraph(
    "<b>Management of steroid-response glaucoma:</b>",
    body_style
))
for item in [
    "Discontinue or taper steroids if clinically feasible",
    "Switch to a weaker steroid (fluorometholone, loteprednol) or steroid-sparing agent (NSAID, cyclosporine)",
    "Add topical IOP-lowering agents (beta-blockers, alpha-agonists, carbonic anhydrase inhibitors, prostaglandin analogues)",
    "Consider trabeculectomy or tube-shunt if IOP remains uncontrolled",
]:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Spacer(1, 0.3*cm))

# 3.2 CATARACT
story.append(Paragraph("3.2 Steroid-Induced Cataract", h2_style))
story.append(Paragraph(
    "Chronic corticosteroid use — topical, systemic, or inhaled — is a well-recognized cause of "
    "<b>posterior subcapsular cataract (PSC)</b>. This is the most characteristic steroid-induced lens change.",
    body_style
))
story.append(Paragraph(
    "Steroids inhibit lens epithelial cell differentiation, alter Na-K ATPase pump function, and may cause "
    "accumulation of water and protein aggregation in the posterior subcapsular region.",
    body_style
))
for item in [
    "Typically bilateral, though may be asymmetric",
    "Patients complain of glare and reduced vision in bright light",
    "PSC is not dose-dependent in a linear fashion — even low doses over long periods can cause it",
    "Children are more susceptible than adults",
    "Systemic steroids (prednisolone > 10–15 mg/day for > 1 year) carry significant risk",
    "In atopic dermatitis — presenile shield-like anterior or PSC cataracts are common and may be exacerbated by long-term steroid therapy",
    "Treatment: Cessation of steroids (does not reverse formed PSC); phacoemulsification + IOL implantation when visually significant",
]:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Spacer(1, 0.3*cm))

# 3.3 SECONDARY INFECTION
story.append(Paragraph("3.3 Masking and Exacerbation of Ocular Infections", h2_style))
story.append(Paragraph(
    "Topical steroids suppress the immune response and can mask or worsen infections:",
    body_style
))
for item in [
    "Herpes simplex keratitis — steroids convert stromal immunity to necrotizing keratitis; geographic ulcers enlarge ('serpentine map'); never use in dendritic epithelial HSV without cover",
    "Fungal keratitis — steroids promote rapid hyphal penetration, suppress neutrophil response; can lead to catastrophic corneal melting",
    "Acanthamoeba keratitis — misdiagnosis and steroid use worsens prognosis significantly",
    "Bacterial keratitis — topical steroids should NOT be initiated by emergency physicians; steroids can accelerate bacterial proliferation",
    "Corneal melting (keratolysis) — steroids inhibit collagenase inhibitors; risk of perforation",
    "Reactivation of latent TB (systemic steroids) — relevant for orbital and posterior segment disease",
]:
    story.append(Paragraph(f"• {item}", bullet_style))
story.append(Paragraph(
    "<b>Rule:</b> Steroids are CONTRAINDICATED in epithelial herpes simplex keratitis (dendritic/geographic ulcer), "
    "fungal keratitis, acanthamoeba keratitis, and bacterial corneal ulcer (without ophthalmologist guidance).",
    warning_style
))

story.append(Spacer(1, 0.3*cm))

# 3.4 CORNEAL EFFECTS
story.append(Paragraph("3.4 Other Corneal Effects", h2_style))
for item in [
    "Delayed corneal wound healing — steroids inhibit fibroblast proliferation and collagen synthesis; important consideration post-PRK, post-keratoplasty",
    "After glaucoma filtering surgery — topical steroids reduce fibroblast infiltration thereby reducing subconjunctival scarring (bleb maintenance — beneficial effect)",
    "Corneal thinning and distortion — with prolonged use in chronic diseases (e.g., herpes zoster ophthalmicus)",
    "Sterile corneal ulcers — with very prolonged use, especially in dry eye disease",
]:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Spacer(1, 0.3*cm))

# 3.5 RETINAL / POSTERIOR EFFECTS
story.append(Paragraph("3.5 Retinal and Posterior Segment Effects", h2_style))
for item in [
    "Central serous chorioretinopathy (CSC) — systemic and topical steroids precipitate/aggravate CSC by altering the fluid balance across the RPE",
    "Intravitreal steroid implants — used therapeutically for CME, uveitis, DME; risk includes IOP elevation and cataract formation",
    "Exudative AMD — exogenous steroids may promote CNV growth; use with caution",
    "Steroid-induced IOP elevation can cause glaucomatous optic nerve damage if undetected",
    "Intravitreal triamcinolone — 'pseudohypopyon' (white precipitate in anterior chamber) can occur as a complication",
]:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Spacer(1, 0.3*cm))

# 3.6 OPTIC NERVE / RAISED ICP
story.append(Paragraph("3.6 Optic Nerve and Raised Intracranial Pressure Effects", h2_style))
for item in [
    "Steroid withdrawal — may precipitate or worsen benign intracranial hypertension (pseudotumor cerebri), causing papilledema",
    "Parenteral steroids for optic neuritis — IV methylprednisolone 1 g/day x 3 days speeds visual recovery but does not improve final visual outcome (ONTT data)",
    "Caution in raised ICP — steroids may paradoxically worsen papilledema on withdrawal",
]:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Spacer(1, 0.4*cm))

# ============================================================
# SECTION 4: SYSTEMIC SIDE EFFECTS
# ============================================================
story.append(section_header("4. SYSTEMIC SIDE EFFECTS OF STEROIDS", RED))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph(
    "Systemic corticosteroids affect virtually every organ system. The severity is related to dose, duration, "
    "and potency of the steroid used. Short courses (10–14 days) carry minimal long-term risk; "
    "chronic use requires vigilant monitoring.",
    body_style
))
story.append(Spacer(1, 0.2*cm))

systemic_se = two_col_table(
    ["System Affected", "Side Effects"],
    [
        ["Hypothalamic-Pituitary-Adrenal (HPA) Axis",
         "Adrenal suppression → Cushing's syndrome (moon face, buffalo hump, central obesity, striae, hirsutism); Adrenal crisis on abrupt withdrawal"],
        ["Metabolic / Endocrine",
         "Hyperglycemia → steroid-induced diabetes; Dyslipidemia; Weight gain; Sodium and water retention; Hypokalaemia"],
        ["Musculoskeletal",
         "Osteoporosis → vertebral/hip fractures; Avascular necrosis (osteonecrosis) of femoral and humeral heads; Proximal myopathy; Myopathy (especially fluorinated steroids)"],
        ["Cardiovascular",
         "Hypertension (fluid retention); Accelerated atherosclerosis; Congestive cardiac failure (fluid overload); Electrolyte imbalances"],
        ["Gastrointestinal",
         "Gastritis; Peptic ulcer disease (potentiated with NSAIDs); GI bleeding; Pancreatitis"],
        ["Immunological / Infections",
         "Immunosuppression → opportunistic infections (TB, fungal, Pneumocystis, CMV); Reactivation of latent TB; Impaired wound healing"],
        ["Psychiatric / CNS",
         "Insomnia; Mood lability and euphoria; Psychosis (steroid psychosis); Depression; Behaviour changes; Pseudotumor cerebri on withdrawal"],
        ["Dermatological",
         "Skin thinning and atrophy; Easy bruising; Poor wound healing; Acne; Hirsutism; Striae distensae"],
        ["Reproductive / Growth",
         "Growth retardation in children; Menstrual irregularities; Reduced fertility"],
        ["Ocular (systemic route)",
         "Posterior subcapsular cataract; Steroid-response glaucoma; Central serous chorioretinopathy"],
    ],
    col_widths=[5*cm, 12*cm]
)
story.append(systemic_se)
story.append(Spacer(1, 0.3*cm))

story.append(info_box(
    "Short-term vs. Long-term Side Effect Profile (Scott-Brown's Otorhinolaryngology)",
    [
        Paragraph("<b>Short-term side effects (common):</b> Gastritis, increased blood sugar, increased appetite, behavioural changes/insomnia/irritability, weight gain, salt and water retention, hypertension.", note_style),
        Paragraph("<b>Long-term / severe side effects:</b> Pancreatitis, GI bleeding, cataracts, myopathy, avascular necrosis of humeral and femoral heads, diabetes mellitus, osteoporosis, opportunistic infections.", note_style),
        Paragraph("<b>Contraindications to systemic steroid use:</b> Insulin-dependent or poorly controlled diabetes, labile hypertension, active tuberculosis, peptic ulcer disease, prior psychiatric reactions to corticosteroids.", note_style),
    ]
))

story.append(Spacer(1, 0.3*cm))

# ============================================================
# SECTION 5: STEROIDS IN SPECIFIC OPHTHALMIC DISEASES
# ============================================================
story.append(section_header("5. STEROIDS IN SPECIFIC OPHTHALMIC CONDITIONS", HexColor("#1a6b3c")))
story.append(Spacer(1, 0.2*cm))

conditions = [
    ("Optic Neuritis", [
        "IV methylprednisolone 1 g/day × 3 days, then oral prednisolone 1 mg/kg/day × 11 days",
        "Speeds visual recovery by approximately 2 weeks (ONTT — Optic Neuritis Treatment Trial)",
        "Does NOT improve final visual acuity at 1 year",
        "Reduces risk of second demyelinating event (MS) in the short-term",
        "Oral prednisolone alone (without IV course) INCREASED the rate of recurrence — avoid",
    ]),
    ("Anterior Uveitis", [
        "Topical prednisolone acetate 1% — 1 drop every 1–2 hours initially, then taper",
        "Plus cycloplegic/mydriatic (atropine, cyclopentolate) to prevent posterior synechiae",
        "Aim: flare 0, cells 0 before tapering steroids",
        "Systemic steroids for bilateral severe or recurrent disease",
    ]),
    ("Posterior Uveitis / Panuveitis", [
        "Sub-Tenon's triamcinolone acetonide injection (40 mg/mL) for unilateral disease",
        "Systemic prednisolone 1 mg/kg/day + immunosuppressives (methotrexate, mycophenolate, azathioprine) for bilateral",
        "Dexamethasone intravitreal implant (Ozurdex 0.7 mg) — approved for non-infectious uveitis",
        "Fluocinolone acetonide implant — for chronic non-infectious posterior uveitis",
    ]),
    ("Diabetic Macular Edema (DME)", [
        "Intravitreal dexamethasone implant (Ozurdex) — for patients who cannot undergo anti-VEGF",
        "Intravitreal triamcinolone — off-label; higher IOP and cataract risk",
        "Fluocinolone acetonide implant (Iluvien) — approved for DME; 3-year sustained release",
        "Anti-VEGF agents (bevacizumab, ranibizumab, aflibercept) are first-line over steroids for DME",
    ]),
    ("Giant Cell Arteritis (GCA)", [
        "MEDICAL EMERGENCY — IV methylprednisolone 500 mg–1 g/day × 3 days",
        "Goal: prevent involvement of fellow eye (risk of bilateral blindness)",
        "Then oral prednisolone 60–80 mg/day with SLOW taper over months to years",
        "Monitor ESR, CRP; temporal artery biopsy confirms diagnosis",
    ]),
    ("Thyroid Eye Disease (TED)", [
        "Active phase (Clinical Activity Score ≥ 3): IV methylprednisolone pulsed therapy (500 mg weekly × 6 weeks, then 250 mg weekly × 6 weeks)",
        "Total cumulative dose should not exceed 8 g",
        "Orbital decompression for compressive optic neuropathy",
        "Inactive phase: Rehabilitative surgery (strabismus, eyelid, decompression)",
    ]),
    ("Allergic Conjunctivitis", [
        "Topical loteprednol etabonate or fluorometholone — preferred for lowest IOP risk",
        "Short-term use (1–2 weeks); not for chronic use",
        "Combine with topical antihistamines and mast cell stabilizers for step-down therapy",
    ]),
]

for cond, points in conditions:
    story.append(Paragraph(cond, h3_style))
    for p in points:
        story.append(Paragraph(f"• {p}", bullet_style))
    story.append(Spacer(1, 0.1*cm))

story.append(Spacer(1, 0.3*cm))

# ============================================================
# SECTION 6: CONTRAINDICATIONS
# ============================================================
story.append(section_header("6. CONTRAINDICATIONS", RED))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph("6.1 Absolute Contraindications (Topical Ocular Steroids)", h2_style))
for item in [
    "Active epithelial herpes simplex keratitis (dendritic/geographic ulcer) — will expand the ulcer dramatically",
    "Fungal keratitis or suspected fungal infection",
    "Acanthamoeba keratitis",
    "Active mycobacterial ocular infections",
    "Vaccinia and varicella keratitis without antiviral cover",
]:
    story.append(Paragraph(f"⚠ {item}", ParagraphStyle("Warn2", parent=bullet_style, textColor=RED)))

story.append(Paragraph("6.2 Relative Contraindications / Caution", h2_style))
for item in [
    "Active bacterial corneal ulcer (only with ophthalmologist supervision and concurrent antibiotic cover)",
    "Glaucoma or family history of glaucoma — monitor IOP closely",
    "Diabetes mellitus (systemic steroids) — risk of loss of glucose control",
    "Peptic ulcer disease — co-prescribe PPI",
    "Osteoporosis — co-prescribe bisphosphonates + calcium + Vitamin D",
    "Active tuberculosis — anti-TB cover required",
    "Prior psychiatric reaction to corticosteroids",
    "Children — higher risk of both cataracts and HPA suppression",
    "Pregnancy — minimal systemic absorption from topical; systemic steroids use with caution",
]:
    story.append(Paragraph(f"• {item}", bullet_style))

story.append(Spacer(1, 0.3*cm))

# ============================================================
# SECTION 7: MONITORING
# ============================================================
story.append(section_header("7. MONITORING DURING STEROID THERAPY", MID_BLUE))
story.append(Spacer(1, 0.2*cm))

monitoring = two_col_table(
    ["Parameter", "Frequency / Notes"],
    [
        ["Intraocular Pressure (IOP)", "Baseline before starting; recheck at 2–4 weeks; then every 4–6 weeks on long-term topical therapy"],
        ["Lens (slit-lamp)", "Baseline; every 6–12 months on chronic therapy; look for PSC"],
        ["Blood glucose", "Baseline; every 2–4 weeks on systemic steroids (especially in diabetics)"],
        ["Blood pressure", "At every visit for patients on systemic steroids"],
        ["Bone mineral density (DEXA)", "Baseline at 3–6 months; annually if on chronic steroids (>3 months)"],
        ["Serum K+ and Na+", "Baseline and periodically for systemic steroids"],
        ["HPA axis (short synacthen test)", "Before planned steroid withdrawal in long-term patients"],
        ["Body weight / BMI", "Monthly for patients on systemic steroids"],
        ["Optic nerve / visual field", "Every 6 months for patients on long-term topical steroids"],
    ],
    col_widths=[5.5*cm, 11.5*cm]
)
story.append(monitoring)
story.append(Spacer(1, 0.3*cm))

# ============================================================
# SECTION 8: KEY EXAM POINTS SUMMARY
# ============================================================
story.append(section_header("8. HIGH-YIELD EXAM SUMMARY TABLE", DARK_BLUE))
story.append(Spacer(1, 0.2*cm))

summary = two_col_table(
    ["Key Point", "Detail"],
    [
        ["Most potent topical steroid", "Difluprednate 0.05% (highest anti-inflammatory & IOP risk)"],
        ["Lowest IOP risk topical steroid", "Loteprednol etabonate (metabolized to inactive metabolites)"],
        ["Steroid-induced cataract type", "Posterior subcapsular cataract (PSC)"],
        ["Steroid glaucoma mechanism", "Reduced TM outflow facility (myocilin upregulation, ECM accumulation)"],
        ["Onset of steroid-response glaucoma", "2–4 weeks (topical); rarely acute (systemic)"],
        ["IOP risk: family history of POAG", "Up to 90% show IOP elevation (vs. 5% in general population)"],
        ["Steroid absolutely contraindicated in", "Epithelial HSV keratitis, fungal keratitis, acanthamoeba"],
        ["Optic neuritis treatment", "IV methylprednisolone 1 g/day × 3 days → speeds recovery, NOT final VA"],
        ["GCA treatment priority", "High-dose IV steroids IMMEDIATELY → prevent fellow eye blindness"],
        ["Systemic Cushingoid feature", "Moon face, buffalo hump, striae, central obesity"],
        ["Post-PRK steroid use", "Topical fluorometholone — reduces haze; used for months"],
        ["Bleb maintenance after trabeculectomy", "Topical steroids reduce fibrosis — prolonged bleb survival"],
        ["Intravitreal steroid for chronic uveitis", "Fluocinolone acetonide implant (Retisert) or Ozurdex"],
        ["Steroid withdrawal danger", "Adrenal crisis; also may unmask pseudotumor cerebri"],
        ["CSC and steroids", "Systemic steroids precipitate/aggravate central serous chorioretinopathy"],
    ],
    col_widths=[6.5*cm, 10.5*cm]
)
story.append(summary)
story.append(Spacer(1, 0.3*cm))

# ============================================================
# REFERENCES
# ============================================================
story.append(HRFlowable(width="100%", thickness=1, color=MID_BLUE, spaceAfter=8))
story.append(Paragraph("References", h2_style))
refs = [
    "Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th ed. — Chapter 74: Ocular Pharmacology (Glucocorticoids section, Table 74-11, 74-12)",
    "Kanski's Clinical Ophthalmology: A Systematic Approach, 10th ed. — Chapter 16: Glaucoma; Chapter 21: Inflammatory Eye Disease",
    "The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease — Chapter 9.9: Steroid-Response Glaucoma",
    "Scott-Brown's Otorhinolaryngology, Head & Neck Surgery, 8th ed. — Chapter 60: Complications of Systemic Steroid Treatment (Box 60.2)",
    "Textbook of Family Medicine, 9th ed. — Glaucoma (Steroid-induced section)",
    "Optic Neuritis Treatment Trial (ONTT) — Comparative evidence on IV vs. oral methylprednisolone for optic neuritis",
]
for i, r in enumerate(refs, 1):
    story.append(Paragraph(f"{i}. {r}", source_style))

story.append(Spacer(1, 0.3*cm))
story.append(Paragraph(
    "Prepared for MS Ophthalmology Examination | August 2026 | Orris Medical Education",
    ParagraphStyle("Footer", parent=styles["Normal"], fontSize=8, textColor=HexColor("#888888"), alignment=TA_CENTER)
))

# ============================================================
# BUILD PDF
# ============================================================
doc.build(story)
print(f"PDF generated: {OUTPUT}")